Contemporary Pediatric Heart Transplant Waitlist Mortality.

BACKGROUND: In 2016, the United Network for Organ Sharing revised its pediatric heart transplant (HT) allocation policy. OBJECTIVES: This study sought to determine whether the 2016 revisions are associated with reduced waitlist mortality and capture patient-specific risks. METHODS: Children listed for HT from 1999 to 2023 were identified using Organ Procurement and Transplantation Network data and grouped into 3 eras (era 1: 1999-2006; era 2: 2006-2016; era 3: 2016-2023) based on when the United Network for Organ Sharing implemented allocation changes. Fine-Gray competing risks modeling was used to identify factors associated with death or delisting for deterioration. Fixed-effects analysis was used to determine whether allocation changes were associated with mortality. RESULTS: Waitlist mortality declined 8 percentage points (PP) across eras (21%, 17%, and 13%, respectively; P < 0.01). At listing, era 3 children were less sick than era 1 children, with 6 PP less ECMO use (P < 0.01), 11 PP less ventilator use (P < 0.01), and 1 PP less dialysis use (P < 0.01). Ventricular assist device (VAD) use was 13 PP higher, and VAD mortality decreased 9 PP (P < 0.01). Non-White mortality declined 10 PP (P < 0.01). ABO-incompatible listings increased 27 PP, and blood group O infant mortality decreased 13 PP (P < 0.01). In multivariable analyses, the 2016 revisions were not associated with lower waitlist mortality, whereas VAD use (in era 3), ABO-incompatible transplant, improved patient selection, and narrowing racial disparities were. Match-run analyses demonstrated poor correlation between individual waitlist mortality risk and the match-run order. CONCLUSIONS: The 2016 allocation revisions were not independently associated with the decline in pediatric HT waitlist mortality. The 3-tier classification system fails to adequately capture patient-specific risks. A more flexible allocation system that accurately reflects patient-specific risks and considers transplant benefit is urgently needed.

Trajectories in Intensity of Medical Interventions at the End of Life: Clustering Analysis in a Pediatric, Single-Center Retrospective Cohort, 2013-2021.

OBJECTIVE: Pediatric deaths often occur within hospitals and involve balancing aggressive treatment with minimization of suffering. This study first investigated associations between clinical/demographic features and the level of intensity of various therapies these patients undergo at the end of life (EOL). Second, the work used these data to develop a new, broader spectrum for classifying pediatric EOL trajectories. DESIGN: Retrospective, single-center study, 2013-2021. SETTING: Four hundred sixty-one bed tertiary, stand-alone children's hospital with 112 ICU beds. PATIENTS: Patients of age 0-26 years old at the time of death. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 1111 included patients, 85.7% died in-hospital. Patients who died outside the hospital were older. Among the 952 in-hospital deaths, most occurred in ICUs (89.5%). Clustering analysis was used to distinguish EOL trajectories based on the presence of intensive therapies and/or an active resuscitation attempt at the EOL. We identified five simplified categories: 1) death during active resuscitation, 2) controlled withdrawal of life-sustaining technology, 3) natural progression to death despite maximal therapy, 4) discontinuation of nonsustaining therapies, and 5) withholding/noninitiation of future therapies. Patients with recent surgical procedures, a history of organ transplantation, or admission to the Cardiovascular ICU had more intense therapies at EOL than those who received palliative care consultations, had known genetic conditions, or were of older age. CONCLUSIONS: In this retrospective study of pediatric EOL trajectories based on the intensity of technology and/or resuscitation discontinued at the EOL, we have identified associations between these trajectories and patient characteristics. Further research is needed to investigate the impact of these trajectories on families, patients, and healthcare providers.

A comprehensive, multifaceted strategy to increase pediatric donor heart utilization.

BACKGROUND: In 2016, we initiated a quality improvement endeavor to increase pediatric heart offer acceptance. This study assessed the effect of these interventions at our center. METHODS: We evaluted pre- and postimplementation cohorts (January 1, 2008-December 31, 2016 vs January 1, 2017-July 1, 2023) comparing donor heart utilization. Six interventions were iterated over time to increase offer acceptance ("extended criteria"): ABO-incompatible transplant, ex vivo perfusion for distanced donors, 3-dimensional total cardiac volume (TCV) assessment, acceptance of hepatitis-C or Severe Acute Respiratory Syndrome Coronavirus 2 infected donors, and institutional culture change favoring consideration of donors previously considered unacceptable. Outcomes studied included annual HT volume, median waitlist duration, sequence number at acceptance, and post-transplant clinical outcomes. RESULTS: During the study period, annual transplant volume increased from 16/year to 25/year pre- and postimplementation. Three hundred thirteen of 389 (80%) listed patients were transplanted. Waitlist duration shortened postimplementation (p = 0.01), as did the percentage of accepted heart offers utilizing at least 1 extended criterion (p < 0.001). Institutional culture change and TCV assessment had the largest impact on donor heart utilization (p = 0.04 and p < 0.001). There was no difference in post-HT intubation or intensive care unit days (p = 0.05-0.9), though post-transplant hospitalization duration (p < 0.001) increased. Post-transplant survival was unaffected by the use of extended criteria hearts (p = 0.3). CONCLUSIONS: We report a successful longitudinal, multifaceted effort to increase organ offer utilization, with institutional culture change and TCV assessments most impactful. The use of extended criteria hearts was not associated with inferior survival.

Neurorehabilitation in a Pediatric Stroke Patient Supported on a CentriMag.

Patients supported on ventricular assist devices (VADs) benefit from rehabilitation while awaiting heart transplantation to recover from surgery, prevent deconditioning, and, in most cases, optimize transplant candidacy. With bleeding and neurological dysfunction as the most common VAD complications, the importance of rehabilitation dramatically increases when a patient on a VAD also suffers from a neurological injury. The rehabilitation needs for cardiac conditioning and neurological reeducation are not the same. Patients with severe neurological deficits require intense rehabilitation that often includes base-of-support challenges, usage of bolsters and balls, partial weight-bearing treadmill training, and assumption of various body positions in prone, kneeling, or quadruped for neuromotor reeducation. However, some devices are more conducive to rehabilitation than others. For children supported by the CentriMag in particular, rehabilitation is challenged by short cannula tubing, an external motor, a large interface, and an intensive care unit (ICU) admission. We report a safe and successful physical therapy course of a pediatric stroke patient with a diagnosis of Ebstein's anomaly supported by a CentriMag right VAD (RVAD) while awaiting heart transplant in the ICU.

Intraoperative and Postoperative Hemodynamic Predictors of Acute Kidney Injury in Pediatric Heart Transplant Recipients.

Acute kidney injury (AKI) is common after pediatric heart transplantation (HT) and is associated with inferior patient outcomes. Hemodynamic risk factors for pediatric heart transplant recipients who experience AKI are not well described. We performed a retrospective review of 99 pediatric heart transplant patients at Lucile Packard Children's Hospital Stanford from January 1, 2015, to December 31, 2019, in which clinical and demographic characteristics, intraoperative perfusion data, and hemodynamic measurements in the first 48 postoperative hours were analyzed as risk factors for severe AKI (Kidney Disease: Improving Global Outcomes [KDIGO] stage ≥ 2). Univariate analysis was conducted using Fisher's exact test, Chi-square test, and the Wilcoxon rank-sum test, as appropriate. Multivariable analysis was conducted using logistic regression. Thirty-five patients (35%) experienced severe AKI which was associated with lower intraoperative cardiac index ( p = 0.001), higher hematocrit ( p < 0.001), lower body temperature ( p < 0.001), lower renal near-infrared spectroscopy ( p = 0.001), lower postoperative mean arterial blood pressure (MAP: p = 0.001), and higher central venous pressure (CVP; p < 0.001). In multivariable analysis, postoperative CVP >12 mm Hg (odds ratio [OR] = 4.27; 95% confidence interval [CI]: 1.48-12.3, p = 0.007) and MAP <65 mm Hg (OR = 4.9; 95% CI: 1.07-22.5, p = 0.04) were associated with early severe AKI. Children with severe AKI experienced longer ventilator, intensive care, and posttransplant hospital days and inferior survival ( p = 0.01). Lower MAP and higher CVP are associated with severe AKI in pediatric HT recipients. Patients, who experienced AKI, experienced increased intensive care unit (ICU) morbidity and inferior survival. These data may guide the development of perioperative renal protective management strategies to reduce AKI incidence and improve patient outcomes.

Survival does not differ by annual center transplant volume-A Pediatric Heart Transplant Society Registry study.

BACKGROUND: There are conflicting data regarding the relationship between center volume and outcomes in pediatric heart transplantation. Previous studies have not fully accounted for differences in case mix, particularly in high-risk congenital heart disease (CHD) groups. We aimed to evaluate the relationship between center volume and outcomes using the Pediatric Heart Transplant Society (PHTS) Registry and explore how case mix may affect outcomes. METHODS: A retrospective cohort study of all pediatric patients in the PHTS Registry who received a heart transplant from 2009 to 2018 was performed. Centers were divided into 5 groups based on average yearly transplant volume. The primary outcome was time to death or graft loss and outcomes were compared using Kaplan-Meier analysis. RESULTS: There were 4583 cases among 55 centers included. There was no difference in time to death or graft loss by center volume in the entire cohort (p = .75), in patients with CHD (p = .79) or in patients with cardiomyopathy (p = .23). There was also no difference in time to death or graft loss by center size in patients undergoing transplant after Norwood, Glenn or Fontan (log rank p = .17, p = .31, and p = .10 respectively). There was a statistically significant difference in outcomes by center size in the positive crossmatch group (p < .0001), though no discernible pattern related to high or low center volume. CONCLUSIONS: Outcomes are similar among transplant centers of all sizes, including for high-risk patient groups with CHD. Future work is needed to understand how patient-specific risk factors may vary among centers of various sizes and whether this influences patient outcomes.

The effect of socioeconomic status on pediatric heart transplant outcomes at a single institution between 2013 and 2022.

BACKGROUND: Disparities in pediatric heart transplant outcomes based on socioeconomic status (SES) have been previously observed. However, there is a need to reevaluate these associations in contemporary settings with advancements in transplant therapies and increased awareness of health disparities. This retrospective study aims to investigate the relationship between SES and outcomes for pediatric heart transplant patients. METHODS: Data were collected through a chart review of 176 pediatric patients who underwent first orthotopic heart transplantation (OHT) at a single center from 2013 to 2021. The Area Deprivation Index (ADI), a composite score based on U.S. census data, was used to quantify SES. Cox proportional hazards models and generalized linear models were employed to analyze the association between SES and graft failure, rejection rates, and hospitalization rates. RESULTS: The analysis revealed no statistically significant differences in graft failure rates, rejection rates, or hospitalization rates between low-SES and high-SES pediatric heart transplant patients for our single-center study. CONCLUSION: There may be patient education, policies, and social resources that can help mitigate SES-based healthcare disparities. Additional multi-center research is needed to identify post-transplant care that promotes patient equity.

An integrated program to expand donor utilization in pediatric heart transplantation: Case report of successful transplant with multiple donor risk factors.

BACKGROUND: Pediatric heart transplantation (HT) continues to be limited by the shortage of donor organs, distance constraints, and the number of potential donor offers that are declined due to the presence of multiple risk factors. METHODS: We report a case of successful pediatric HT in which multiple risk factors were mitigated through a combination of innovative donor utilization improvement strategies. RESULTS: An 11-year-old, 25-kilogram child with cardiomyopathy and pulmonary hypertension, on chronic milrinone therapy and anticoagulated with apixaban, was transplanted with a heart from a Hepatitis C virus positive donor and an increased donor-to-recipient weight ratio. Due to extended geographic distance, an extracorporeal heart preservation system (TransMedics™ OCS Heart) was used for procurement. No significant bleeding was observed post-operatively, and she was discharged by post-operative day 15 with normal biventricular systolic function. Post-transplant Hepatitis C virus seroconversion was successfully treated. CONCLUSIONS: Heart transplantation in donors with multiple risk factor can be achieved with an integrative team approach and should be taken into consideration when evaluating marginal donors in order to expand the current limited donor pool in pediatric patients.

Long-term kidney outcomes in pediatric continuous-flow ventricular assist device patients.

BACKGROUND: Continuous-flow ventricular assist devices (CF-VADs) are used increasingly in pediatric end-stage heart failure (ESHF) patients. Alongside common risk factors like oxidant injury from hemolysis, non-pulsatile flow constitutes a unique circulatory stress on kidneys. Post-implantation recovery after acute kidney injury (AKI) is commonly reported, but long-term kidney outcomes or factors implicated in the evolution of chronic kidney disease (CKD) with prolonged CF-VAD support are unknown. METHODS: We studied ESHF patients supported > 90 days on CF-VAD from 2008 to 2018. The primary outcome was CKD (per Kidney Disease Improving Global Outcomes (KDIGO) criteria). Secondary outcomes included AKI incidence post-implantation and CKD evolution in the 6-12 months of CF-VAD support. RESULTS: We enrolled 134 patients; 84/134 (63%) were male, median age was 13 [IQR 9.9, 15.9] years, 72/134 (54%) had preexisting CKD at implantation, and 85/134 (63%) had AKI. At 3 months, of the 91/134 (68%) still on a CF-VAD, 34/91 (37%) never had CKD, 13/91 (14%) developed de novo CKD, while CKD persisted or worsened in 49% (44/91). Etiology of heart failure, extracorporeal membrane oxygenation use, duration of CF-VAD, AKI history, and kidney replacement therapy were not associated with different CKD outcomes. Mortality was higher in those with AKI or preexisting CKD. CONCLUSIONS: In the first multicenter study to focus on kidney outcomes for pediatric long-term CF-VAD patients, preimplantation CKD and peri-implantation AKI were common. Both de novo CKD and worsening CKD can happen on prolonged CF-VAD support. Proactive kidney function monitoring and targeted follow-up are important to optimize outcomes.

Reducing donor acceptance practice variation - Learnings from a discussion forum.

PURPOSE: Although waitlist mortality is unacceptably high, nearly half of donor heart offers are rejected by pediatric heart transplant centers. The Advanced Cardiac Therapy Improving Outcome Network (ACTION) and Pediatric Heart Transplant Society (PHTS) convened a multi-institutional donor decision discussion forum (DDDF) aimed at assessing donor acceptance practices and reducing practice variation. METHODS: A 1-h-long virtual DDDF for providers across North America, the United Kingdom, and Brazil was held monthly. Each session typically included two case presentations posing a real-world donor decision challenge. Attendees were polled before the presenting center's decision was revealed. Group discussion followed, including a review of relevant literature and PHTS data. Metrics of participation, participant agreement with presenting center decisions, and impact on future decision-making were collected and analyzed. RESULTS: Over 2 years, 41 cases were discussed. Approximately 50 clinicians attended each call. Risk factors influencing decision-making included donor quality (10), size discrepancy (8), and COVID-19 (8). Donor characteristics influenced 63% of decisions, recipient factors 35%. Participants agreed with the decision made by the presenting center only 49% of the time. Post-presentation discussion resulted in 25% of participants changing their original decision. Survey conducted reported that 50% respondents changed their donor acceptance practices. CONCLUSION: DDDF identified significant variation in pediatric donor decision-making among centers. DDDF may be an effective format to reduce practice variation, provide education to decision-makers, and ultimately increase donor utilization.

Supplemental nutrition, feeding disorders, and renourishment in pediatric heart failure through transplantation.

BACKGROUND: Tube feeds are used commonly in children listed for heart transplant; however, rates of renourishment and development of feeding disorders are not sufficiently characterized. METHODS: Retrospective review of pediatric heart transplant recipients from January 1, 2014, to January 3, 2021. Demographics, anthropometric, and nutritional data were collected from heart transplant listing through 3 years post-transplant. Renourishment rates, presence of a feeding disorder, and need for a gastric feeding tube were analyzed. Multivariable analysis was conducted to identify risks for poor nutritional outcomes. RESULTS: Of 104 patients, 35 (34%) and 36 (35%) were malnourished at heart transplant listing and transplant, respectively, persisting in 21/91 (23%) 1 year postheart transplant. Forty (38%) received tube feeds at listing, 42 (40%) at heart transplant, and 18/90 (20%) 1 year post-transplant. Rates of feeding disorders fell from 23% at transplantation to 10% 1 year post-transplant. Feeding disorders were associated with younger age at heart transplant (p < .001) and congenital heart disease (p = .03). Forty-six percent of infants required a gastric feeding tube. Renourishment occurred in 20% during listing and was associated with ventricular assist device support (p = .03) and noncalorically dense feeds (p = .03). Malnutrition at transplant was associated with inferior post-transplant survival (6/36 (17%) vs. 2/68 (3%); p = .02). CONCLUSIONS: Malnourishment requiring tube feeds is common in pediatric heart transplant candidates; however, most patients who eventually survive to transplant remain malnourished at time of transplantation and 1 year later. While some children develop feeding disorders, they generally resolve by 1 year post-transplant.

A novel acute kidney injury scoring system for renal and clinical outcomes in pediatric heart transplant patients.

BACKGROUND: The development of acute kidney injury (AKI) has been associated with worse outcomes in children after heart transplantation. Our study compares the application of a cumulative six-point Kidney Diseases Improving Global Outcomes (KDIGO) AKI scoring system, utilizing both creatinine and urine output criteria that we term as the AKI-6 criteria, to traditional AKI staging as a predictor for clinical and renal outcomes in the pediatric heart transplant recipients. METHODS: We conducted a retrospective single-center chart review on 155 pediatric patients who underwent heart transplantation from May 2014 to December 2021. The primary independent variable was the presence of severe AKI. Severe AKI by KDIGO was defined as Stage ≥2, whereas severe AKI by AKI-6 was defined as cumulative scores ≥4 or Stage 3 AKI based on either KDIGO criterion alone. Primary outcomes included actuarial survival and renal dysfunction by 1-year post-transplant, defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2 . RESULTS: In total, 140 (90%) patients developed AKI; 98 (63%) patients developed severe AKI by KDIGO, and 60 (39%) by AKI-6. Severe AKI by AKI-6 was associated with worse actuarial survival following heart transplantation compared with KDIGO (p = 0.01). Of the 143 patients with 1-year creatinine data, 6 (11%) patients out of 54 with severe AKI by AKI-6 had evidence of renal dysfunction (p = 0.01), compared with 6 (7%) patients out of 88 by KDIGO (p = 0.3). CONCLUSIONS: AKI-6 scoring provides greater prognostic utility for actuarial survival and renal dysfunction by 1-year post-heart transplantation in pediatric patients than traditional KDIGO staging.

Outcomes After Development of Ventricular Arrhythmias in Single Ventricular Heart Disease Patients With Fontan Palliation.

BACKGROUND: With the advent of more intensive rhythm monitoring strategies, ventricular arrhythmias (VAs) are increasingly detected in Fontan patients. However, the prognostic implications of VA are poorly understood. We assessed the incidence of VA in Fontan patients and the implications on transplant-free survival. METHODS: Medical records of Fontan patients seen at a single center between 2002 and 2019 were reviewed to identify post-Fontan VA (nonsustained ventricular tachycardia >4 beats or sustained >30 seconds). Patients with preFontan VA were excluded. Hemodynamically unstable VA was defined as malignant VA. The primary outcome was death and heart transplantation. Death with censoring at transplant was a secondary outcome. RESULTS: Of 431 Fontan patients, transplant-free survival was 82% at 15 years post-Fontan with 64 (15%) meeting primary outcome of either death (n=16, 3.7%), at a median 4.6 (0.4-10.2) years post-Fontan, or transplant (n=48, 11%), at a median of 11.1 (5.9-16.2) years post-Fontan. Forty-eight (11%) patients were diagnosed with VA (90% nonsustained ventricular tachycardia, 10% sustained ventricular tachycardia). Malignant VA (n=9, 2.0%) was associated with younger age, worse systolic function, and valvular regurgitation. Risk for VA increased with time from Fontan, 2.4% at 10 years to 19% at 20 years. History of Stage 1 surgery with right ventricular to pulmonary artery conduit and older age at Fontan were significant risk factors for VA. VA was strongly associated with an increased risk of transplant or death (HR, 9.2 [95% CI, 4.5-18.7]; P<0.001), with a transplant-free survival of 48% at 5-year post-VA diagnosis. CONCLUSIONS: Ventricular arrhythmias occurred in 11% of Fontan patients and was highly associated with transplant or death, with a transplant-free survival of <50% at 5-year post-VA diagnosis. Risk factors for VA included older age at Fontan and history of right ventricular to pulmonary artery conduit. A diagnosis of VA in Fontan patients should prompt increased clinical surveillance.

The teammate trial: Study design and rationale tacrolimus and everolimus against tacrolimus and MMF in pediatric heart transplantation using the major adverse transplant event (MATE) score.

BACKGROUND: Currently there are no immunosuppression regimens FDA-approved to prevent rejection in pediatric heart transplantation (HT). In recent years, everolimus (EVL) has emerged as a potential alternative to standard tacrolimus (TAC) as the primary immunosuppressant to prevent rejection that may also reduce the risk of cardiac allograft vasculopathy (CAV), chronic kidney disease (CKD) and cytomegalovirus (CMV) infection. However, the 2 regimens have never been compared head-to-head in a randomized trial. The study design and rationale are reviewed in light of the challenges inherent in rare disease research. METHODS: The TEAMMATE trial (IND 127980) is the first multicenter randomized clinical trial (RCT) in pediatric HT. The primary purpose is to evaluate the safety and efficacy of EVL and low-dose TAC (LD-TAC) compared to standard-dose TAC and mycophenolate mofetil (MMF). Children aged <21 years at HT were randomized (1:1 ratio) at 6 months post-HT to either regimen, and followed for 30 months. Children with recurrent rejection, multi-organ transplant recipients, and those with an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2 were excluded. The primary efficacy hypothesis is that, compared to TAC/MMF, EVL/LD-TAC is more effective in preventing 3 MATEs: acute cellular rejection (ACR), CKD and CAV. The primary safety hypothesis is that EVL/LD-TAC does not have a higher cumulative burden of 6 MATEs (antibody mediated rejection [AMR], infection, and post-transplant lymphoproliferative disorder [PTLD] in addition to the 3 above). The primary endpoint is the MATE score, a composite, ordinal surrogate endpoint reflecting the frequency and severity of MATEs that is validated against graft loss. The study had a target sample size of 210 patients across 25 sites and is powered to demonstrate superior efficacy of EVL/LD-TAC. Trial enrollment is complete and participant follow-up will be completed in 2023. CONCLUSION: The TEAMMATE trial is the first multicenter RCT in pediatric HT. It is anticipated that the study will provide important information about the safety and efficacy of everolimus vs tacrolimus-based regimens and will provide valuable lessons into the design and conduct of future trials in pediatric HT.

International practice heterogeneity in pre-transplant management of pulmonary hypertension related to pediatric left heart disease.

BACKGROUND: Elevated pulmonary vascular resistance (PVR) in the setting of left heart failure may contribute to poor outcomes after pediatric heart transplant (HTx), but peri-transplant management is variable. METHODS: We sought to characterize international practice by surveying physicians at pediatric HTx centers. RESULTS: We received 49 complete responses from 39 centers in 16 countries. Most respondents are pediatric cardiologists (90%), practice at centers offering heart (86%) and lung (55%) transplant, and perform pre-HTx acute vasoreactivity testing (AVT, 88%) in patients with elevated PVR. Half (51%) reported defining a PVR cutoff for HTx eligibility as ≤6 WU m2 (56%) post-AVT (84%). The highest post-AVT PVR ever accepted for HTx ranged from 3-14.4 (median 6) WU m2 . To treat elevated pre-transplant PVR, phosphodiesterase type 5 inhibitors are most common (65%) followed by oxygen (31%), nitric oxide (14%), endothelin receptor antagonists (11%), and prostacyclins (6%). Nearly a third (31%) do not routinely use pulmonary vasodilators without implantation of a left ventricular assist device (LVAD). Case scenarios highlight treatment variability: in a restrictive cardiomyopathy scenario, HTx listing with post-transplant vasodilator therapy was favored, whereas in a Shone's complex patient with fixed PVR, LVAD ± pulmonary vasodilators followed by repeat catheterization was most common. Management of dilated cardiomyopathy with reactive PVR was variable. Most continue vasodilator therapy until HTx (16%), PVR normalizes (16%) or ≤6 months. CONCLUSIONS: Management of elevated PVR in children awaiting HTx is heterogenous. Evidence-based guidelines are needed to allow for longitudinal determination of optimal outcomes and standardized care.

Increased risk of infections in pediatric Fontan patients after heart transplantation.

BACKGROUND: Infectious complications are a major cause of morbidity and mortality after HT. Fontan patients may be more susceptible to post-HT infections. METHODS: This was a single-center, retrospective cohort analysis of pediatric patients undergoing HT for FF physiology or DCM, who underwent induction with ATG. The primary endpoint was an infection in the first 180 days post-HT, defined as positive (1) blood/urine/respiratory culture; (2) viral PCR; (3) skin or wound infection; and/or (4) culture-negative infection if ≥5 days of antibiotics were completed. Secondary endpoints included (1) cell counts after ATG; (2) PTLD; and (3) rejection (≥Grade 2R ACR or pAMR2) in the first 180 days post-HT. RESULTS: A total of 59 patients (26 FF, 33 DCM) underwent HT at 14.7 (IQR 10.6, 19.5) and 11.7 (IQR 1.4, 13.6) years of age, respectively. The median total ATG received was 7.4 (IQR 4.9, 7.7) vs 7.5 (IQR 7.3, 7.6) mg/kg (p = NS) for FF and DCM patients, respectively. Twenty-three patients (39%) developed an infection 180 days post-HT, with a higher rate of infection in FF patients (54% vs 27%, p = .03). Adjusted for pre-transplant absolute lymphocyte count, FF patients had a higher risk of infection at 30 days post-HT (OR 7.62, 95% CI 1.13-51.48, p = .04). There was no difference in the incidence of PTLD (12% vs 0%; p = .08) or rejection (12% vs 21%; p = .49). CONCLUSION: Compared to DCM patients, FF patients have a higher risk of infection. Modifications to induction therapy for FF patients should be considered.

Sixth Annual Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs) Report: The Society Of Thoracic Surgeons Pedimacs Annual Report.

BACKGROUND: The Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs), supported by The Society of Thoracic Surgeons, provides detailed information on pediatric patients supported with ventricular assist devices (VADs). METHODS: From September 19, 2012, to December 31, 2021, there were 1355 devices in 1109 patients (<19 years) from 42 North American Hospitals. RESULTS: Cardiomyopathy was the most common underlying cause (59%), followed by congenital heart disease (25%) and myocarditis (9%). Regarding device type, implantable continuous (IC) VADs were most common at 40%, followed by paracorporeal pulsatile (PP; 28%) and paracorporeal continuous (PC; 26%). Baseline demographics differed, with the PC cohort being younger, smaller, more complex (ie, congenital heart disease), and sicker at implantation (P < .0001). At 6 months after VAD implantation, a favorable outcome (transplantation, recovery, or alive on device) was achieved in 84% of patients, which was greatest among those on IC VADs (92%) and least for PC VADs (69%). Adverse events were not uncommon, with nongastrointestinal bleeding (incidence of 14%) and neurologic dysfunction (11% [stroke, 4%]), within 2 weeks after implantation being the most prevalent. Stroke and bleeding had negative impacts on overall survival (P = .002 and P < .001, respectively). CONCLUSIONS: This Sixth Pedimacs Report demonstrates the continued evolution of the pediatric field. The complexity of cardiac physiologies and anatomic constraint mandates the need for multiple types of devices used (PC, PP, IC). Detailed analyses of each device type in this report provide valuable information to further advance the care of this challenging and vulnerable population.

End-of-Life in Pediatric Patients Supported by Ventricular Assist Devices: A Network Database Cohort Study.

OBJECTIVES: Most pediatric patients on ventricular assist device (VAD) survive to transplantation. Approximately 15% will die on VAD support, and the circumstances at the end-of-life are not well understood. We, therefore, sought to characterize patient location and invasive interventions used at the time of death. DESIGN: Retrospective database study of a cohort meeting inclusion criteria. SETTING: Thirty-six centers participating in the Advanced Cardiac Therapies Improving Outcomes Network (ACTION) Registry. PATIENTS: Children who died on VAD therapy in the period March 2012 to September 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 117 of 721 patients (16%) who died on VAD, the median (interquartile range) age was 5 years (1-16 yr) at 43 days (17-91 d) postimplant. Initial goals of therapy were bridge to consideration for candidacy for transplantation in 60 of 117 (51%), bridge to transplantation in 44 of 117 (38%), bridge to recovery 11 of 117 (9%), or destination therapy (i.e., VAD as the endpoint) in two of 117 (2%). The most common cause of death was multiple organ failure in 35 of 117 (30%), followed by infection in 12 of 117 (10%). Eighty-five of 92 (92%) died with a functioning device in place. Most patients were receiving invasive interventions (mechanical ventilation, vasoactive infusions, etc.) at the end of life. Twelve patients (10%) died at home. CONCLUSIONS: One-in-six pediatric VAD patients die while receiving device support, with death occurring soon after implant and usually from noncardiac causes. Aggressive interventions are common at the end-of-life. The ACTION Registry data should inform future practices to promote informed patient/family and clinician decision-making to hopefully reduce suffering at the end-of-life.