Search

Background: Ventricular assist devices (VADs) are used to bridge pediatric patients to heart transplantation. Paracorporeal VADs require the placement of cannulas, which can create an environment for infections. We examined cannula infections in pediatric VAD patients and the role of nutritional status. Methods: This retrospective study (2005–2021) included patients <20 years old on VAD support using Berlin Heart EXCOR® cannulas. Cannula infections were defined by a positive culture and need for antibiotic therapy. Malnutrition was defined using the American Society of Parenteral and Enteral Nutrition guidelines as well as the Michigan MTool. Results: There were 76 patients with a median age at implant of 0.9 years (IQR 0.4, 3.6), 50% male, with 73.7% having non‐congenital heart disease. More than one‐quarter (26.3%) of patients developed a cannula infection. Higher pre‐implant weight (OR = 1.93, p = 0.05), creatinine (OR = 1.02, p = 0.044), and pre‐albumin (OR = 15.79, p = 0.025), as well as duration of VAD support (OR = 1.01; p = 0.003) were associated with increased odds of developing a cannula infection. There was no difference in the malnutrition parameters between those with and without an infection. Conclusions: Further exploration in a larger cohort is needed to see whether these associations remain and if the incorporation of objective measures of nutritional status at the time of infection are predictive. [ABSTRACT FROM AUTHOR]

Background: The Pediatric Heart Transplant Society (PHTS) Registry was founded 30 years ago as a collaborative effort among like‐minded providers of this novel life‐saving technique for children with end‐stage heart failure. In the intervening decades, the data from the Registry have provided invaluable knowledge to the field of pediatric heart transplantation. This report of the PHTS Registry provides a comprehensive look at the data, highlighting both the longevity of the registry and one unique aspect of the PHTS registry, allowing for exploration into children with single ventricle anatomy. Methods: The PHTS database was queried from January 1, 1993 to December 31, 2019 to include pediatric (age < 18 years) patients listed for HT. For our analysis, we primarily analyzed patients by era. The early era was defined as children listed for HT from January 1, 1993 to December 31, 2004; middle era January 1, 2005 to December 31, 2009; and recent era January 1, 2010 to December 31, 2019. Outcomes after listing and transplant, including mortality and morbidities, are presented as unadjusted for risk, but compared across eras. Results: Since 1993, 11 995 children were listed for heart transplant and entered into the PHTS Registry with 9755 listed during the study period. The majority of listings occurred within the most recent era. Waitlist survival improved over the decades as did posttransplant survival. Other notable changes over time include fewer patients experiencing allograft rejection or infection after transplant. Waitlist and posttransplant survival have changed dramatically in patients with single ventricle physiology and significantly differ by stage of single ventricle palliation. Summary: Key points from this PHTS Registry summary and focus on patients with single ventricle congenital heart disease in particular, include the changing landscape of candidates and recipients awaiting heart transplant. There is clear improvement in waitlist and transplant outcomes for children with both cardiomyopathy and congenital heart disease alike. [ABSTRACT FROM AUTHOR]

Background: Pediatric patients awaiting a heart transplant have high waitlist mortality. Several strategies have been utilized to decrease waiting times, but a mortality risk still exists. New medical technologies may improve waiting times and associated mortality. Ex situ heart perfusion (ESHP) is one such technology, which can decrease the impact of cold ischemia on the donor heart and allow for a longer out‐of‐body time. Adoption of such technology in pediatric heart transplantation will require support from end users, including patient and families. The aim of this qualitative study was to report the perspectives of families with experience related to pediatric HTx toward ESHP. Methods: Semistructured interviews were conducted with 12 parents or guardians of children who were awaiting or received heart transplantation. Interviews were transcribed, and data were analyzed using qualitative content analysis. Results: Participants expressed varied awareness and knowledge of ESHP. Independent of their understanding of ESHP, all purported that ESHP was an excellent idea and that this technology should be implemented in the pediatric population. They did not identify fundamentally different ethical issues or concerns for ESHP being used relative to other medical technologies. Overall, most participants described consent processes for ESHP should be like any other procedure. All agreed that the surgeon should continue to describe the overall health of the donor heart, provide their medical recommendations, and allow families to have the final say. Conclusions: The concepts described by the parents and guardians are important in moving this novel technology forward. This information will serve the basis for knowledge translation that will provide educational resources to broaden the understanding and reach of ESHP. [ABSTRACT FROM AUTHOR]

Background: Short‐term continuous flow (STCF) ventricular assist devices (VADs) are utilized in adults with cardiogenic shock; however, mortality remains high. Previous studies have found that high pre‐operative MELD‐XI scores in durable VAD patients are associated with mortality. The use of the MELD‐XI score to predict outcomes in STCF‐VAD patients has not been explored. We sought to determine the relationship between MELD‐XI and outcomes in adults with STCF‐VADs. Methods: This was a retrospective review of adults implanted with STCF‐VADs between 2009 and 2019. Receiver operating characteristic (ROC) analysis was performed to predict outcomes and Kaplan–Meier analysis was done to assess survival. Results: Seventy‐nine patients were included with a median MELD‐XI score of 21.2 (IQR 13.5, 27.0). Patients with an unsuccessful wean from support (p < 0.001) or major post‐operative bleeding (p = 0.03) had significantly higher pre‐implant MELD‐XI scores. The optimal MELD‐XI cut‐point for mortality was 24.9 with 27.8 for major bleeding. Survival was worse among patients in the high‐risk MELD‐XI group, however, not statistically significant (p = 0.09). Prior ECMO support, but not MELD‐XI, was an independent predictor of unsuccessful wean (p = 0.03). Conclusions: Pre‐operative MELD‐XI score was a moderate predictor of unsuccessful wean with limited utility in predicting bleeding in patients on STCF‐VAD support. This scoring system may be useful in the clinical setting for pre‐implant risk stratification and counseling among patients and outcomes. [ABSTRACT FROM AUTHOR]

Background: ABO‐incompatible heart transplantation (HTx) has become a standard procedure for children below 2 years of age due to an immunologically immature immune system and associated low isohemagglutinin titers. Methods: We report a case of an ABO‐incompatible HTx (recipient blood group O, donor blood group A) at the age of 5 years and 11 months with a fully matured immune system and previously high isohemagglutinin titers that diminished as a result of human leucocyte antigen (HLA) desensitization therapy with rituximab and immunoglobulins. Results: The anti‐A titer at the time of HTx was 1:16 with post‐transplant isoagglutinin titers never exceeding 1:4 without any signs of rejection with now 3 years of post‐HTx follow‐up. Conclusions: ABO isohemagglutinin titers should be routinely assessed in children undergoing desensitization therapy since ABOi transplantation can be considered in selected cases to expand the donor pool with the option of crossing the ABO barrier to find a better‐matched allograft. [ABSTRACT FROM AUTHOR]

Background: Children with heart failure have the highest mortality while awaiting transplantation. Ex situ heart perfusion (ESHP), a method for continuous perfusion of the donor heart, has the potential to improve access to transplant by increasing travel distance between donor and recipient. An adult ESHP device is currently available, but as of yet there is no pediatric device. The aim of this study was to evaluate current knowledge of ESHP among pediatric heart transplant practitioners, define potential barriers, and identify uses of this novel technology. Methods: An electronic survey was developed to assess perspectives of international pediatric heart transplant stakeholders (n = 68) on ESHP. Select questions were analyzed to evaluate for associations between groups of respondents and patterns of response. Results: Most respondents were familiar but <10% had clinically utilized ESHP. There was optimism that ESHP could decrease waitlist mortality. Respondents were concerned about potential device malfunction and lack of long‐term outcomes. There were no differences found in terms of ESHP familiarity among age groups, practitioner center volume, country of work, or discipline. Conclusions: ESHP has the potential to expand the pediatric heart donor pool and decrease waitlist mortality. More education on outcomes and risks/benefits is needed in order to promote widespread adoption. [ABSTRACT FROM AUTHOR]

Background: Despite efforts, pediatric HTx candidates continue to have high waitlist mortality due to limited donor availability. However, there is a significant number of offered hearts not used due to concerns of viability. ESHP is a method for continuous perfusion of the donor heart that allows assessment and extended out‐of‐body time. It is imperative to understand healthcare stakeholders' perspectives on ESHP for implementation. Therefore, the aims of this qualitative study were to: (1) Explore pediatric stakeholders' perspectives toward ESHP; and (2) Identify barriers to widespread adoption of this technology. Methods: Virtual focus groups were completed with pediatric HTx healthcare professional stakeholders. Following transcription of audio‐recordings, the material was analyzed using content analysis. Results: Four focus groups were completed with 17 participants, representing 12 institutions and three countries. Focus groups revealed varied understanding of both current and potential uses of ESHP. Participants did see the potential benefits of extending out‐of‐body time for and the ability to evaluate donor heart quality. However, concerns were expressed relating to patient selection, wait‐list times, post‐HTx outcomes, adverse events, and technical issues. These were felt to be important to understand in order to justify the costs of ESHP and impact on the healthcare system. Conclusions: This project represents the first qualitative formative evaluation of ESHP in pediatrics. The knowledge gained from stakeholders will form the basis for education initiatives, clinical trial design, and roll‐out of new ESHP technologies designed for pediatrics. [ABSTRACT FROM AUTHOR]

Background: Single‐ventricle patients require a series of surgeries, with the final stage being the Fontan. This form of circulation results in several long‐term complications, but the impact and consequences of nutrition status remain unclear. We sought to evaluate the incidence of malnutrition in Fontan patients and the impact on outcomes. Methods: This study was a retrospective cohort study of children who underwent Fontan surgery between 1997 and 2018. Clinical, demographic, and nutrition data were collected, including weight, height, body mass index (BMI), and their respective z scores (z score for weight‐for‐age [WAZ], z score for height‐for‐age [HAZ], and z score for BMI‐for‐age [BMIZ]) pre‐Fontan, at discharge, 6 months, and 1, 5, and 10 years post‐Fontan. Malnutrition status was categorized using the American Society for Parenteral and Enteral Nutrition guidelines and the Michigan MTool. Fontan failure was defined as listing for heart transplant or death. Results: Of the 69 patients, moderate‐severe malnutrition occurred at any time point in 11% (n = 8) by WAZ, 16% (n = 11) by HAZ, and 6% (n = 4) by BMIZ. Moderate‐severe malnutrition persisted in 6.5%–12.9% at 10 years post‐Fontan. Compared with the pre‐Fontan period, there was no change in these parameters over time. There was no statistically significant difference in Fontan failure between degrees of pre‐Fontan malnutrition. Conclusion: There is a 6%–16% incidence of moderate‐severe malnutrition in Fontan patients. Malnutrition is a condition that remains present in follow‐up. There was no association with anthropometric parameters and transplant‐free survival. A prospective multi‐institutional study is needed to understand the impact of malnutrition on long‐term outcomes. [ABSTRACT FROM AUTHOR]

Objective: This document is designed to outline the definition, pathogenesis, diagnostic modalities and therapeutic measures to treat antibody‐mediated rejection in children postheart transplant Methods: Literature review was conducted by a Pediatric Heart Transplant Society (PHTS) working group to identify existing pediatric and adult studies on antibody‐mediated rejection (AMR). In addition, the centers participating in PHTS were asked to submit their approach to diagnosis and management of pediatric AMR. This document synthesizes information gathered from both these sources to highlight a practical approach to diagnosing and managing a child with AMR postheart transplant. This document may not represent the practice at all centers in the PHTS and serves as a starting point to understand an approach to this clinical scenario. [ABSTRACT FROM AUTHOR]

Background: Early detection of cardiac allograft rejection is crucial for post‐transplant graft survival. Despite the progress made in immunosuppression strategies, acute cellular rejection remains a serious complication during and after the first post‐transplant year, and there is a continued lack of consensus regarding its treatment, especially in pediatric transplant patients. Methods: An open request was placed via the listserv to the membership of the Pediatric Heart Transplant Society (PHTS). Along with a broad literature search, numerous institutional protocols were pooled, analyzed and consolidated. A clinical approach document was generated highlighting areas of consensus and practice variation. Results: The clinical approach document divides cellular rejection by International Society for Heart and Lung Transplantation grades and provides management strategies for each, including persistent cellular rejection. Conclusions: Cellular rejection treatment can be tailored to the clinical status, graft function, and the grade of cellular rejection. A case of mild and asymptomatic rejection may not require treatment, whereas a higher‐grade rejection or rejection with graft dysfunction or hemodynamic compromise may require aggressive intravenous therapies, changes to maintenance immunosuppression therapy and augmented surveillance. [ABSTRACT FROM AUTHOR]

This manuscript outlines a clinical approach to vasoplegia incorporating the current state of knowledge regarding vasoplegia in pediatric patients immediately post‐transplant and to identify modifiable factors both pre‐ and post‐transplant that may reduce post‐operative morbidity, end‐organ dysfunction, and mortality. Centers participating in the Pediatric Heart Transplant Society (PHTS) were asked to provide their internal protocols and rationale for vasoplegia management, and applicable adult and pediatric data were reviewed. The authors synthesized the above protocols and literature into the following description of clinical approaches to vasoplegia highlighting areas of both broad consensus and of significant practice variation. [ABSTRACT FROM AUTHOR]

The use of mechanical circulatory support (MCS) for pediatric patients who have undergone heart transplant has grown rapidly in the past decade. This includes support in the immediate post‐transplant period and "rescue" therapy for patient later in their transplant course. Extracorporeal membrane oxygenation (ECMO) remains a standard modality of support for intraoperative concerns and for acute decompensation in the immediate post‐transplant period. However, both pulsatile and continuous flow ventricular assist devices (VADs) have been used with increasing success in transplant patients for longer durations of support. Centers participating in the Pediatric Heart Transplant Society (PHTS) were queried to provide their internal protocols and rationale for mechanical circulatory support following heart transplant. These protocols coupled with evidence‐based literature were used to provide the following description of clinical approaches to MCS in the transplant patient highlighting areas of both broad consensus and significant practice variation. [ABSTRACT FROM AUTHOR]

Background: VAD support for early graft failure after HTx is a rare event in pediatrics. Methods: We retrospectively describe our single‐center experience with post‐HTx VAD support in a cohort of patients transplanted between 01/05 and 12/20. Results: Nine patients underwent VAD insertion in the early post‐HTx period [median age 6.1 years (Range 0.3–20.3), median weight 17.6 kg (Range 3.5–65.0), and congenital heart disease (67%)]. Of the nine patients with early graft failure, almost half (44%) were implanted after 2015 and all of these patients had a pre‐HTx plan for possible post‐transplant VAD insertion. Time to VAD implant was a median of 0 day (Range 0–11). Total time on VAD support was a median of 12 days (Range 3.0–478.0). Two‐thirds (n = 6; 67%) of the patients were weaned from support, retransplanted (11%) and two patients died (22%). In all of the patients where post‐HTx VAD was anticipated there was 100% survival. Conclusions: In this small patient series, post‐HTx VAD was a useful measure in selected patients especially with pre‐HTx planning. However, more shared experiences to verify these findings are needed. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Heart transplantation (HTx) is a treatment option for end‐stage heart failure in children. HTx is limited by the availability and acceptability of donor hearts. Refusal of donor hearts has been reported to be common with reasons for refusal including preexisting donor characteristics. This review will focus on the impact of donor characteristics and comorbidities on outcomes following pediatric HTx. A literature review was performed to identify articles on donor characteristics and comorbidities and pediatric HTx outcomes. There are many donor characteristics to consider when accepting a donor heart. Weight‐based matching is the most common form of matching in pediatric HTx with a donor‐recipient weight ratio between 0.7 and 3 having limited impact on outcomes. From an age perspective, donors <50 years can be carefully considered, but the impact of ischemic time needs to be understood. To increase the donor pool, with minimal impact on outcomes, ABO‐incompatible donors should be considered in patients that are eligible. Other factors to be considered when accepting an organ is donor comorbidities. Little is known about donor comorbidities in pediatric HTx, with most of the data available focusing on infections. Being aware of the potential infections in the donor, understanding the testing available and risks of transmission, and treatment options for the recipient is essential. There are a number of donor characteristics that potentially impact outcomes following pediatric HTx, but these need to be taken into consideration along with their interactions with recipient factors when interpreting the outcomes following HTx. [ABSTRACT FROM AUTHOR]

It has long been recognized that there is significant variation in the way that centers approach clinical management and problems within pediatric transplantation. This has recently been highlighted in two publications by the PHTS showing practice variation in both surveillance for cardiac allograft vasculopathy and diagnosis of acute rejection. These differences in practice are important to recognize and serve as the foundation for collaborative learning, developing research questions, and implementing quality improvement initiatives. To further understand the practice variation within the society, and to begin the process of learning from each other, the society has developed a Clinical Approach Working Group, whose task is to tackle issues seen in transplant and integrate current literature with clinical protocols and experience from the individual sites. The early work of this group has results in the series of Clinical approach articles presented in this issue of Pediatric Transplantation. [ABSTRACT FROM AUTHOR]

A VAD is a mechanical pump used to support the functioning of a failing heart. As a pediatric therapy, a VAD is used as a temporary solution for poor heart function, a bridge to transplantation or recovery, or a destination therapy. The goal of this qualitative study was to explore the perspectives of family and professional caregivers of children who are supported by VADs in outpatient settings. Semi-structured interviews were conducted with 22 caregivers of school-aged children discharged home on VAD support. Interviews were transcribed, and data were analyzed using qualitative content analysis. Caregivers identified issues facing children on VAD support in the contexts of home, school, and other childhood places including being physically connected to a device; experiencing changes; living a medical life; negotiating restrictions; cost of care; family, kinship, and community; and, present and future living. While a child with a VAD may have much in common with other medically complex children, the technological complications and risks of living with a VAD are uniquely identified by caregivers as an issue, especially when considering the way that children with a VAD are connected to their device-implanted yet exterior, mobile yet restricted, and autonomous yet dependent. [ABSTRACT FROM AUTHOR]

Eosinophilia has been rarely reported in pediatric heart transplant recipients and has been suggested to play a role in graft rejection. We report a case of a young female patient with peripheral blood eosinophilia who died suddenly 2 years following ABO-incompatible heart transplantation. She was found at autopsy to have myocardial infiltration of not only T-lymphocytes and macrophages expected in acute cellular rejection but also of eosinophils, B-lymphocytes, and plasma cells indicating myocarditis. [ABSTRACT FROM AUTHOR]

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

Iron overload cardiomyopathy secondary to β-thalassemia major is a potentially reversible condition managed with chelation and medical hemodynamic support, as bridge-to-recovery or transplant. We describe our experience, and challenges faced, in a pediatric patient with iron overload cardiomyopathy secondary to β-thalassemia major, requiring biventricular MCS. [ABSTRACT FROM AUTHOR]

Organ availability and acceptability limit pediatric HTx. What characteristics define an unacceptable or high-risk pediatric donor remains unclear. The purpose of this study was to characterize a large cohort of pediatric donors and determine the donor risk factors, including cumulative risk, that affect recipient survival. Data from the PHTS, a prospective multicenter study, were used to examine the impact of donor factors on the outcomes of patients listed <18 yr of age who received a HTx between 1993 and 2009. Donor data were available for 3149 of 3156 HTx (99.8%). Donor cause of death, need for inotropes, or CPR did not affect survival outcomes (p = 0.05). Ischemic time also did not have an impact on overall recipient survival; however, longer ischemic times negatively impacted one-yr post-transplant survival (p < 0.0001). There was no impact of cumulative risk factors on survival (p = 0.8). Although used in a minority of cases, hormonal therapy in the donor positively impacted survival (p = 0.03). In multivariate analysis, the only donor factor associated with decreased survival was smaller donor BSA, the other factors being related to the recipient characteristics. When analyzed by recipient age, there were no donor-related factors that affected survival for those who received a transplant at <6 months of age. Longer ischemic time (p < 0.0001) and greater age difference between the recipient and donor (p = 0.0098) were donor-related factors impacting early-phase survival for recipients who received a graft at ≥10 yr of age. Factors perceived to define a marginal or high-risk pediatric heart donor including inotrope use, CPR and donor cause of death may have less impact on outcomes than previously thought. Longer ischemic times did impact one yr, but not overall survival, and this impact was much greater with older donors. Parameters for accepting a donor heart can potentially be expanded, especially in the infant age group, but strong consideration should always be given to the interaction between ischemic time and donor age. [ABSTRACT FROM AUTHOR]

Background: The use of ventricular assist devices (VADs) in children with heart failure may be of particular benefit to those with accompanying renal failure, as improved renal function is seen in some, but not all recipients. We hypothesized that persistent renal dysfunction at 7 days and/or 1 month after VAD implantation would predict chronic kidney disease (CKD) 1 year after heart transplantation (HT). Methods: Linkage analysis of all VAD patients enrolled in both the PEDIMACS and PHTS registries between 2012 and 2016. Persistent acute kidney injury (P‐AKI), defined as a serum creatinine ≥1.5× baseline, was assessed at post‐implant day 7. Estimated glomerular filtration rate (eGFR) was determined at implant, 30 days thereafter, and 12 months post‐HT. Pre‐implant eGFR, eGFR normalization (to ≥90 mL/min/1.73 m2), and P‐AKI were used to predict post‐HT CKD (eGFR <90 mL/min/1.73 m2). Results: The mean implant eGFR was 85.4 ± 46.5 mL/min/1.73 m2. P‐AKI was present in 19/188 (10%). Mean eGFR at 1 month post‐VAD implant was 131.1 ± 62.1 mL/min/1.73 m2, significantly increased above baseline (P < 0.001). At 1 year post‐HT (n = 133), 60 (45%) had CKD. Lower pre‐implant eGFR was associated with post‐HT CKD (OR 0.99, CI: 0.97‐0.99, P = 0.005); P‐AKI was not (OR 0.96, CI: 0.3‐3.0, P = 0.9). Failure to normalize renal function 30 days after implant was highly associated with CKD at 1 year post‐transplant (OR 12.5, CI 2.8‐55, P = 0.003). Conclusions: Renal function improves after VAD implantation. Lower pre‐implant eGFR and failure to normalize renal function during the support period are risk factors for CKD development after HT. [ABSTRACT FROM AUTHOR]

The author reflects on concerns over the bioequivalence of the clinical implications of the use of generic immunosuppression (IS) in adults, who are recipients of an organ transplant. Topics discussed include a study on the survival, adverse events and rejection of generic IS, a study on tacrolimus blood concentrations, and understanding the clinical significance of generic IS.

HTx in neonates is mainstay therapy for those with severe cardiomyopathies and congenital heart disease. Fetal listing for HTx has been proposed as a way to increase the potential window for a donor with outcomes predicted to be similar to the neonatal population. Data from the PHTS, a prospective multicenter study, were used to examine the outcomes of fetuses listed between 1993 and 2009. Four thousand three hundred and sixty-five children were listed for HTx during this period. Fetuses comprised 1% and neonates 19.8% of listed patients. In those patients listed as fetus and transplanted, the median wait time from listing to HTx was 55 days (range 4-255), with a median of 25 days (range 0-233) after birth. By six months post-listing, a higher proportion of fetal listed patients had undergone HTx with a lower waitlist mortality when compared with neonate. There was no significant difference in survival following HTx between the two group (p = 0.4). While the results of this study may be less applicable to current practice due to changes in referrals for fetal listing, they do indicate that fetal listing can be a reasonable option. These results are of particular interest at the present time given the ongoing public discourse on the proposed elimination of fetal listing within UNOS. [ABSTRACT FROM AUTHOR]