Pediatric Cardiac Transplantation Research Articles

Cardiac catheterization activity in pediatric cardiac transplantation. Can catheterization needs be predicted?

Cardiac catheterization activity in pediatric cardiac transplantation. Can catheterization needs be predicted?

The Effect of Neurodevelopmental Disorders on the Prognosis of Children Undergoing Heart Transplantation: A Retrospective Analysis of the National Inpatient Sample 2011–2019

Background: Many international governing bodies recommend against heart transplantation in patients with severe cognitive-behavioral disabilities, however no clear criteria are offered to define severity. Patients with neurodevelopmental disorders may face systematic discrimination when being evaluated for transplant. We set out to investigate whether children with neurodevelopmental disorders that undergo heart transplantation have poorer in-hospital outcomes compared to neurotypical children. Methods: A retrospective analysis of the National Inpatient Sample database was conducted to identify pediatric patients with neurodevelopmental disorders who underwent heart transplantation from 2011–2019. Baseline characteristics and in-hospital outcomes between patients were compared. Binary logistic regression was used to investigate the association between the documented presence of a neurodevelopmental disorder and in-hospital outcomes in children undergoing heart transplantation. Results: We identified a weighted sample of 3770 pediatric cardiac transplant patients, of whom 245 (6.5%) had a documented diagnosis of neurodevelopmental disorder. There was no significant difference in the odds of major adverse cardiovascular events (all-cause mortality, stroke complications or myocardial infarction), surgical complications, infection, venous thromboembolic events, delirium/restraint use, or cardiac dysrhythmia. Patients with neurodevelopmental disorders had lower overall length of stay (44.0 days interquartile range (IQR): 16.0–90.0 vs. 57.08 days IQR: 22.0–112.0, p < 0.050), and cost of stay ($956,031 IQR: 548,559.0–1,801,412.0 vs. $1,074,793 IQR: 599,089.8–2,129,086.0, p < 0.050). Patients with neurodevelopmental disorders had significantly lower odds of acute transplant complications (adjusted odds ratio (aOR): 0.39, 95% confidence interval (CI): 0.21–0.74, p < 0.050) vascular complications (aOR: 0.36, 95% CI: 0.19–0.66, p < 0.050) and acute kidney injury (AKI) (aOR: 0.52, 95% CI: 0.33–0.83, p < 0.050). Conclusions: These data suggest that patients with neurodevelopmental disorders have overall similar if not potentially improved post-transplant outcomes in the acute setting compared to neurotypical patients, possibly secondary to selection bias in the patient selection process.

Contemporary outcomes of pediatric cardiac transplantation with a positive retrospective crossmatch.

A positive crossmatch (+ XM) has traditionally been associated with adverse outcomes following pediatric heart transplantation. However, more recent studies suggest that favorable intermediate-term outcomes may be achieved despite a + XM. This study's hypothesis is that children with a + XM have similar long-term survival, but higher rate of complications such as rejection, coronary allograft vasculopathy (CAV), and infection, compared to patients with a negative (-) XM. The Pediatric Heart Transplant Society Registry (PHTS) database was queried from 2010-2021 for all patients <18 years of age with a known XM. Baseline demographics were compared between + XM and - XM groups using appropriate parametric and non-parametric group comparisons. Cox Proportional Hazards Modeling was used to identify risk factors for post-transplant graft loss, rejection, and CAV. Of 4599 pediatric heart transplants during the study period, XM results were available for 3914 (85%), of which 373 (9.5%) had a + XM. Univariate analysis showed lower 10-year survival for patients with + XM (HR = 1.3, p = .04). Multivariate analyses revealed no significant difference in 10-year survival in the 2 groups; however, time to first rejection (p = .0001) remained significantly shorter in the + XM group. Pediatric patients transplanted across a + XM experience earlier rejection; however, after multivariate adjustment, + XM is not independently associated with intermediate-term graft loss. The risk of heart transplantation against a + XM must be balanced with the ongoing risk of waitlist mortality.

Differences in Baseline Immunophenotype in Pediatric Cardiac Transplant Evaluation: How Informed Reductions in Immunosuppression can Improve Patient Outcomes

Lifelong multi-drug immunosuppression is essential in pediatric cardiac transplant with regimens varying between pediatric centers. Current data suggests pre-transplant immunologic phenotype differences may predispose patients to over-immunosuppression. At our tertiary care center, targeted reduction of immunosuppression has recently become common practice despite limited published data. We hypothesize that individualized reduction of immunosuppression in pediatric cardiac transplant patients based on baseline immunophenotype will lead to improved outcomes post-transplant.From January 2020 through July 2022, 52 pediatric patients were referred to our tertiary care center for cardiac transplant evaluation, which includes Immunology evaluation. Patient demographics, cardiac history, and pre-transplant immune evaluation (T/B/NK cell quantitation, quantitative immunoglobulins, vaccine responses and T cell functional testing, as available) were collected. Genetic testing was reviewed. 28 patients who completed cardiac transplant were followed up to 12 months for information on reduced immunosuppression (decreased/bypassed induction with antithymocyte globulin and/or decreased long-term immunosuppression goals), infections, and rejection post-transplant.Of patients referred for evaluation, 63% had congenital heart disease (CHD). Nearly 100% of CHD patients required cardiac surgery in the first year of life with thymectomy. Of all referred patients and of those with available total T cell count (CD3+ T cells), 54% were lymphopenic (CD3+ T cells < 1000/mm3), and 11% of the lymphopenic children were severely lymphopenic (CD3+ T cells < 300/mm3). Patient IgG levels outside of protein losing enteropathy (PLE) and vaccine responses were within normal limits. Available microarray results showed 5 children with abnormal chromosomal syndromes (including 22q11.2 deletion syndrome). Of those referred, 28 patients underwent cardiac transplant and review of outcomes for up to 12 months post-transplant is on-going.Immunologic abnormalities are inconsistent in cardiac patients and may be secondary to early thymectomy, PLE or chromosomal deletion syndromes. Our data demonstrates significant differences in pre-transplant immunologic phenotypes and will add to the limited literature on decreasing immunosuppression in severely lymphopenic cardiac patients. This retrospective study provides encouragement for partnership between immunology and cardiology teams to conduct larger, prospective multicenter studies to further understand individualization of immunosuppression regimens, the role of baseline immunophenotyping to inform these decisions and the resulting improvement in transplant outcomes.

Modifications to therapeutic plasma exchange to achieve rapid exchange on cardiopulmonary bypass prior to pediatric cardiac transplant.

Cardiac transplants increasingly occur following placement of ventricular assist devices (VADs). A strong association exists between human leukocyte antigen (HLA) sensitization and VAD placement; however, desensitization protocols that utilize therapeutic plasma exchange (TPE) are fraught with technical challenges and are at increased risk of adverse events. In response to increased VAD utilization in our pre-transplant population, we developed a new institutional standard for TPE in the operating room. Through a multidisciplinary effort, we developed an institutional protocol for intraoperative TPE immediately prior to cardiac transplantation after cannulation onto cardiopulmonary bypass (CPB). All procedures used the standard TPE protocol on the Terumo Optia (Terumo BCT, Lakewood, CO, USA), but incorporated multiple modifications to limit patients' bypass times, and to coordinate with the surgical teams. These modifications included deliberate misidentification of replacement fluid and maximization of the citrate infusion rate. These adjustments allowed the machine to run at maximal inlet speeds, minimizing duration of TPE. To date, 11 patients have been treated with this protocol. All survived their cardiac transplantation operation. Hypocalcemia and hypotension were noted; however, none of these adverse events appeared to have clinical impact. Technical complications included unexpected fibrin deposition in the TPE circuit and air in the inlet line due to surgical manipulation of the CPB cannula. No thromboembolic complications occurred in any patient. We feel that this procedure can be rapidly and safely performed in HLA sensitized pediatric patients on CPB to limit the risk of antibody mediated rejection of their heart transplant.

Xenotransplantation: A historical-ethical account of viewpoints.

Formal clinical trials of pig-to-human organ transplant-known asxenotransplantation-may begin this decade, with the first trials likely to consist of either adult renal transplants or pediatric cardiac transplant patients. Xenotransplantation as a systematic scientific study only reaches back to the latter half of the 20th century, with episodic xenotransplantation events occurring prior to that. As the science of xenotransplantation has progressed in the 20th and 21st centuries, the public's knowledge of the potential therapy has also increased. With this, there have been shifting ethical stances toward xenotransplantation in key areas, such as religious and public viewpoints towards xenotransplantation, animal rights, and public health concerns. This review provides a historical-ethical account of xenotransplantation and details if or how viewpoints have shifted over time.

Rethinking status 1A criteria in pediatric cardiac transplantation: A case for the prioritization of patients with single ventricle anatomy supported by ventricular assist devices.

Over the past 2 years advancements in the techniques and technology of pediatric heart transplantation have exponentially increased. However, even as the number of pediatric donor hearts has grown, demand for this limited resource continues to far outpace supply. Thus, lifesaving support in the form of ventricular assist devices (VAD) has become increasingly utilized in bridging pediatric patients to cardiac transplant. In the current pediatric heart transplant listing criteria, adopted by the United Network for Organ Sharing (UNOS) in 2016, all pediatric patients with a VAD are granted 1A status and assigned top transplant priority regardless of their underlying pathology. However, should this be the case? We suggest that the presence of a VAD alone may not be sufficient for status 1A listing. In doing so, we specifically highlight the heightened acuity, resource utilization, risk profile, and diminished outcomes in patients with single ventricle physiology supported with VAD as compared to patients with structurally normal hearts who would both be listed under 1A status. Given this, from a distributive justice perspective, we further suggest that the lack of granularity in current pediatric cardiac transplant listing categories may inadvertently lead to an inequitable distribution of donor organs and hospital resources especially as it pertains to those with single ventricle anatomy on VAD support. We propose revisiting the current listing priorities in light of improved techniques, technology, and recent data to mitigate this phenomenon. By doing this, pediatric patients with single ventricle disease might be more equitably stratified while awaiting heart transplant.

Impact of race and health coverage on listing and waitlist mortality in pediatric cardiac transplantation

Social factors like race and insurance affect transplant outcomes. However, little is known in pediatric heart transplantation. We hypothesized that race and insurance coverage impact listing and waitlist outcomes across eras. Data from the Pediatric Heart Transplant Society multi-center registry prospectively collected between January 1, 2000-December 31, 2019 were analyzed. Patients were divided by race as Black, White and other and by insurance coverage at listing (US governmental, US private and non-US single payer systems (UK, Canada). Clinical condition at listing and waitlist outcomes were compared across races and insurance coverages. Categorical variables were compared using a chi-square test and continuous variables using the Wilcoxon rank sum test. Risk factors for waitlist mortality were examined using multiphase parametric hazard modeling. A sensitivity analysis using parametric hazard explored the interaction between race and insurance. At listing, compared to Whites (n=5391) and others (n = 1167), Black patients (n=1428) were older, more likely on US governmental insurance and had cardiomyopathy as the predominant diagnosis (p < 0.0001). Black patients were more likely to be higher status at listing, in hospital, on inotropes or a ventricular assist device (p < 0.0001). Black patients had significantly shorter time on the waitlist compared to other races(p < 0.0001) but had higher waitlist mortality (p=0.0091), driven by the earlier era (2000-2009) (p=0.0005), most prominently within the US private insurance cohort (p=0.015). Outcomes were not different in other insurance cohorts or in the recent era (2010-2019). Black children are older and sicker at the time of listing, deteriorate more often and face a higher wait list mortality, despite a shorter waitlist period and favorable clinical factors, with improvement in the recent era associated with the recent US healthcare reforms. The social construct of race appears to disadvantage Black children by limiting referral, consideration or access to pediatric cardiac transplantation.

Race and Socioeconomic Bias in Pediatric Cardiac Transplantation

BackgroundTo date, no studies evaluated implicit bias among clinicians caring for children with advanced heart failure. ObjectivesThis study aims to evaluate implicit racial and socioeconomic bias among pediatric heart transplant clinicians. MethodsA cross-sectional survey of transplant clinicians from the Pediatric Heart Transplant Society was conducted between June and August 2021. The survey consisted of demographic questions along with explicit and validated race and socioeconomic status (SES) implicit association tests (IATs). Implicit and explicit biases among survey group members were studied and associations were tested between implicit and explicit measures. ResultsOf 500 members, 91 (18.2%) individuals completed the race IAT and 70 (14%) completed the SES IAT. Race IAT scores indicated moderate levels of implicit bias (mean = 0.33, d = 0.76; P < 0.001; ie, preference for White individuals). SES IAT scores indicated strong implicit bias (mean = 0.52, d = 1.53; P < 0.001; ie, preference for people from upper SES). There were weak levels of explicit race and wealth bias. There was a strong level of explicit education bias (mean = 5.22, d = 1.19; P < 0.001; ie, preference for educated people). There were nonsignificant correlations between the race and the SES IAT and explicit measures (P > 0.05 for all). ConclusionsAs observed across other health care disciplines, among a group of pediatric heart transplant clinicians, there is an implicit preference for individuals who are White and from higher SES, and an explicit preference for educated people. Future studies should evaluate how implicit biases affect clinician behavior and assess the impact of efforts to reduce such biases.

Association of Donors With US Public Health Service Risk Criteria and Outcomes After Adult vs Pediatric Cardiac Transplant

The United Network for Organ Sharing (UNOS) evaluates donor risk for acute transmission of HIV, hepatitis B, or hepatitis C based on US Public Health Services (PHS)-specific criteria. However, recent data regarding use and outcomes of those donors with PHS risk criteria among pediatric and adult heart transplant recipients are lacking. To compare use and outcomes of graft from donors with PHS risk criteria vs those with a standard-risk donor (SRD) in children vs adults in a contemporary cohort. This cohort was a nationwide analysis of heart transplants in the US that used data from the UNOS database. Participants were children (<18 years old) and adults (≥18 years old) who received a heart transplant from January 1, 2010, to December 31, 2021. UNOS-defined donor risk status. Trend analysis compared changes in PHS risk criteria use among children and adults. Patient survival was analyzed using Kaplan-Meier curves with log rank and Cox proportional hazards to compare PHS risk-criteria outcomes vs SRD-criteria outcomes in children and adult heart transplant recipients. Additional analysis was performed among adults who received a PHS-risk criteria graft that was previously declined for pediatric recipients. Of 5115 pediatric transplant recipients (donor without PHS risk median [IQR] age, 5 [0-13] years and donor with PHS risk median [IQR] age, 8 [0-14] years) and 30 289 adult heart transplant recipients (donor without PHS risk median [IQR] age, 56 [46-63] years and donor with PHS risk median [IQR] age, 57 [47-63] years), PHS risk criteria comprised 8% in children vs 25% in adults. PHS criteria are being increasingly used over the past decade with the proportion of recipients transplanted with PHS risk-criteria donors being approximately 3 times greater among adult recipients than children recipients. Pediatric recipients of a PHS risk-criteria donor had greater pretransplant ventilatory support, whereas adult recipients of a PHS risk-criteria donor had greater pretransplant extracorporeal membrane oxygenation use. Patient survival was similar between pediatric recipients of PHS risk-criteria grafts vs SRD-criteria grafts and slightly higher among adult recipients of PHS risk-criteria grafts vs SRD-criteria grafts. The 1778 adult recipients who received a PHS criteria-risk donor that was previously declined for pediatric recipients had similar patient survival recipients compared with SRD-criteria donors (HR, 0.92; 95% CI, 0.81-1.03; P = .18). In the current era, a 3-fold greater proportion of adult recipients receive a PHS risk-criteria graft compared with children despite similar posttransplant patient survival. The ongoing organ donor shortage underscores the need for consideration of PHS risk criteria where these donors remain underused.

Prognostic Value of Exercise Stress Echocardiography in Pediatric Cardiac Transplant Recipients

Cardiac allograft vasculopathy (CAV) is a leading cause of long-term morbidity and mortality in pediatric heart transplant (HTx) recipients. Exercise stress echocardiography (ESE) has been shown to be useful in the detection of angiographically confirmed coronary artery disease in children. However, the prognostic utility of ESE for prediction of cardiac events in HTx survivors is unknown. We aim to assess whether an abnormal (positive) ESE is be associated with a higher risk of future cardiovascular (CV) outcomes in pediatric HTx recipients. We conducted a retrospective review of CV outcomes in a cohort of 95 pediatric HTx recipients who underwent 188 ESEs over a 10-year period. A composite endpoint for CV events including myocardial infarction, hospitalization for nonrejection heart failure, coronary revascularization, need for repeat transplantation, and death was used. Based on the interpretation of the ESE results, each ESE study was classified for this study as either positive (abnormal) or negative (normal) for ischemia. Results of the coronary angiograms performed near the time of ESE were also assessed and classified for this study as positive (abnormal) or negative (normal) for CAV according to standard HTx criteria for CAV. Fifty-one (27%) ESEs were positive for ischemia. There was a total of 35 CV events in 23 patients. A positive ESE was associated with increased risk of any CV event (hazard ratio=3.55; 95% CI, 1.52, 8.28), as well as an increased risk of CV death (hazard ratio=3.19; 95% CI, 1.23, 8.28). Freedom from composite CV outcome at 1, 2, and 3years following a positive ESE was 89.9% (95% CI=77.3%, 95.7%), 81.5% (95% CI=65.9%, 90.5%), and 63.2% (95% CI=41.9%, 78.5%), respectively. Freedom from composite CV outcome at 1, 2, and 3years following a negative ESE was 99.3% (94.8, 99.9), 98.4% (93.6, 99.6), and 97.0% (90.6, 99.1), respectively. No patient died within 1year of a negative ESE. In this largest study of ESE in pediatric HTx recipients, a positive or abnormal ESE is associated with increased future CV morbidity and mortality. Conversely, a negative ESE can help predict CV event-free survival. Even in the setting of a normal coronary angiogram, our pilot data show that an abnormal ESE may still be clinically important. Use of ESE in follow-up may improve risk stratification and management of pediatric HTx recipients.

Racial and Ethnic Disparities in Incidence and Prognosis of Perioperative Stroke Among Pediatric Cardiac Transplant Recipients.

Background In the general population, Black children have a higher incidence of stroke and all-cause mortality after stroke than White children. Beginning 6 months following cardiac transplantation, Black children have higher mortality than White children. However, whether there are racial and ethnic disparities in incidence and all-cause mortality following perioperative stroke among pediatric cardiac transplant recipients is unknown. Methods and Results Using the Scientific Registry of Transplant Recipients, we studied children who underwent their first heart transplant in the United States between January 1994 and September 2019. Using multivariable logistic regression, we assessed the association between race and ethnicity and perioperative stroke. We used multivariable piecewise Cox regression to examine the association between race and ethnicity and mortality among survivors of perioperative stroke. Among 8224 children who had a first cardiac transplant, 255 (3%) had a perioperative stroke. Black children had 32% lower odds of perioperative stroke compared with White children (adjusted odds ratio, 0.68 [95% CI, 0.46-0.996]). Following perioperative stroke, mortality rates were similar for Black and White children in the first 6months (adjusted hazard ratio [HR], 0.99 [95% CI, 0.44-2.26]). However, Black children had a higher mortality rate than White children beyond 6 months (adjusted HR, 3.36 [95% CI, 1.22-9.22]). Conclusions Among pediatric cardiac transplant recipients, Black children have a lower incidence of perioperative stroke than White children. Among survivors of perioperative stroke, mortality is initially similar by race and ethnicity, but beyond 6 months, Black children have over a 3-fold higher mortality rate than White children. Identifying and intervening on potential differences in care is essential to addressing these disparities.

COVID-19-induced silent myocarditis and newly developed hypertension in a 3-year-old boy

BackgroundCOVID-19 myocarditis occurs in 7–28% of patients admitted in the hospital with or without multisystem inflammatory syndrome. It may present as fulminant myocarditis. Dilated cardiomyopathy as a sequela of COVID-19 myocarditis has been reported in the pediatric population. However, to date, no case of silent COVID-19 myocarditis progressing to dilated cardiomyopathy has been reported in children. Furthermore, although newly developed hypertension as a sequela of COVID-19 infection has been reported in adults, there is no report of newly developed COVID-induced hypertension in children. We report a 3-year-old boy with silent COVID-19 myocarditis progressing to dilated cardiomyopathy and newly developed systemic hypertension.Case presentationA 3-year-old boy was referred to the emergency department because of respiratory distress. The parents gave a history of SARS-CoV-2 infection in the child 5 months ago that was manifested as fever and cough, for which he was treated as an outpatient. Echocardiographic examination revealed a severe decrease in left ventricular systolic function in favor of dilated cardiomyopathy. Cardiac magnetic resonance imaging established the diagnosis of myocarditis. The patient left ventricular systolic function did not improve after 2 weeks of intravenous inotropic support. Therefore, the child was transferred to another tertiary center with extracorporeal membrane oxygenation and pediatric cardiac transplantation facilities.ConclusionsCOVID-19 can induce silent myocarditis with progression to dilated cardiomyopathy and newly developed systemic hypertension. Thus, a thorough examination of the heart and measurement of blood pressure are mandatory in every child with COVID-19 infection. Cardiac MR is an indispensable tool in the diagnosis, follow-up, and prognostication of COVID-19 myocarditis. Moreover, four-chamber speckle tracking strain imaging showed apical rocking in all the four heart chambers in this child with opposite direction in the failed left ventricle compared with other cardiac chambers. Lastly, the presence of septal flash on M-mode echocardiography, apical rocking and prestretch–rebound stretch patterns on longitudinal strain imaging of the failed left ventricle in this child may be of predictive value for response to cardiac resynchronization therapy.

Early Complication of Monomorphic B-cell Lymphoma Post Pediatric Cardiac Transplantation

<h3>Introduction</h3> Post-transplant lymphoproliferative disorder (PTLD) occurs in 5% to 10% of all pediatric transplant recipients and is an important cause of post-transplant morbidity and mortality. Subtypes include reactive plasmocytic, monomorphic (e.g. B-cell lymphoma), and polymorphic forms. The most common type is monomorphic and is most often associated with Epstein Barr Virus. <h3>Case Report</h3> We describe a case of severe monomorphic B-cell lymphoma PTLD presenting 5 months post-transplant in a 15-year-old male with dilated cardiomyopathy. Both donor and recipient were seropositive for EBV. Peak EBV log post-transplant was 4.08. He received standard induction therapy with anti-thymocyte globulin and routine post-transplant immunosuppression with standard dosing of tacrolimus, mycophenolic acid, and steroid. His post-operative course was complicated by sternal osteomyelitis treated with 3 months of Ertapenem. Early biopsies revealed ACR 1R, but no significant rejection episodes or hemodynamic compromise. He presented with fever, abdominal pain, sore throat, and bilateral ear pain 5 months post-transplant. PET/MRI scan confirmed PTLD within tonsils, adenoids, and a focal hepatic lesion. A monomorphic high grade B-cell lymphoma was identified. Given these findings, his tonsils and adenoids were removed and immunosuppression regimen reduced. He received 4 weekly doses of Rituximab. Repeat PET scan demonstrated increased interval size of the hepatic lesion and new pulmonary nodules. Due to disease persistence, he was treated with four cycles of DA-EPOCH chemotherapy (etoposide, vincristine, doxorubicin, cyclophosphamide, and prednisone). PET scan 7 months post initial presentation demonstrated disease recurrence of the adenoid/tonsillar tissue. Biopsy of the nasal sinus by endoscopy revealed a rare aberrant B-cell population including CD19, CD20, CD22, and CD23. He required 2 additional cycles of chemotherapy and continues to undergo treatment of his PTLD. <h3>Summary</h3> PTLD is a known complication post-cardiac transplantation. Risk factors include EBV-naivety, degree of immunosuppression, and host genetic variations. Treatment is typically reduction in immunosuppression. We describe an extreme case of PTLD not responsive to immunosuppression reduction or rituximab alone and highlight the need for alternative treatment strategies for more advanced disease.

Abstract WP172: Racial Disparities In Perioperative Stroke And Mortality Following Stroke Among Pediatric Cardiac Transplant Recipients

Introduction: In the general population, Black children have a higher incidence of stroke and all-cause mortality after stroke. Following cardiac transplantation, mortality is similar across Black and white children within the first 6 months, but Black children have higher mortality beyond 6 months. However, whether there are racial disparities in incidence and all-cause mortality following perioperative stroke among pediatric cardiac transplant recipients is unknown. Methods: Using the Scientific Registry of Transplant Recipients, we examined all children in the United States with their first heart transplant from January 1994-September 2019. We used multivariable logistic regression to assess the association between race and perioperative stroke. We used Kaplan Meier survival curves and multivariable piecewise Cox proportional hazard regression to examine the association between race and mortality among children who survived a perioperative stroke. Results: Among 8,224 children who had a first cardiac transplant, 255 (3%) had a perioperative stroke. Black children had a 32% lower odds of perioperative stroke compared to white children (OR=0.68, 95%CI 0.46-0.996). In unadjusted and multivariable-adjusted analyses, survival was similar for Black and white children in the first 6 months following perioperative stroke (Figure 1a, adjusted HR = 1.13, 95%CI 0.57-1.83), however Black children had a lower survival probability compared to white children beyond 6 months (Figure 1b, adjusted HR = 3.21, 95%CI 1.19-8.69, log-rank p=0.017). Conclusion: Among pediatric cardiac transplant recipients, Black children have a lower incidence of perioperative stroke than white children. Following perioperative stroke during cardiac transplantation, mortality is similar by race, but beyond 6 months, Black children have a higher mortality rate than white children. Intervening on potential differences in care is essential to addressing these disparities.

Paediatric dilated cardiomyopathy with and without endocardial fibroelastosis - a pathological analysis of 89 explants.

Heart failure due to dilated cardiomyopathy is a major indication for paediatric cardiac transplantation. Endocardial fibroelastosis is a recognised pathological finding of unknown prognostic significance in paediatric dilated cardiomyopathy. To evaluate the nature of the association between left ventricular endocardial fibroelastosis and paediatric dilated cardiomyopathy, we reviewed surgical pathology reports of dilated cardiomyopathy explants (1986-2016) in order to characterise the pathological findings and to compare and contrast their frequency among four age groups: less than 1 year; 1-5 years; 6-10 years; and greater than 11 years. The 89 explants (47 males and 42 females) were all characterised by increased weight and left ventricular chamber dilatation without increased wall thickness. Ninety-five per cent of the specimens in the two youngest subsets had left ventricular endocardial fibroelastosis. Compared to the oldest age group, recipients aged 1-5 years had a 6-fold increase and those younger than 1 year a 19-fold increase in the odds of observing left ventricular endocardial fibroelastosis. Explants with and without endocardial fibroelastosis were otherwise phenotypically similar. In paediatric dilated cardiomyopathy endocardial fibroelastosis is a very common pathological finding, especially in infants and young children. We propose that the descriptive, clinico-pathological designation "Dilated Cardiomyopathy with Endocardial Fibroelastosis" should be adopted to facilitate future investigation into the potential prognostic/therapeutic significance of left ventricular endocardial fibroelastosis.

Current opinion in pediatric heart transplantation.

Cardiac transplant remains the most effective therapy for children with end-stage heart disease. Outcomes remain better than any alternative therapy for this condition, but its use is limited by donor organ availability. As a result, waitlist times and mortality on the waiting list remain unacceptably high. Novel approaches are necessary to address this problem. Organ Procurement and Transplant Network/United Network for Organ Sharing readjusted the pediatric heart allocation system in 2016 to prioritize children at highest risk of mortality, encourage judicious listing, and improve appropriate donor organ utilization. Subsequent studies have aligned with these priorities to help risk-stratify patients at the time of listing and identify the importance that should be assigned to donor-specific factors. In addition, many authors are advocating for increased utilization of hearts donated after cardiac death. Pediatric Ventricular Assist Device (VAD) application has also been increasing to help decrease waitlist mortality. Although results have significantly improved, there remain important limitations to widespread use of VADs in the pediatric population. This has prompted novel techniques such as pulmonary artery banding to improve cardiac function and, in some cases, promote recovery. The demand for cardiac replacement continues to increase with an ageing population of patients with congenital heart disease, presenting new challenges and stressors to the system. Pediatric cardiac transplant outcomes are excellent but remain plagued by the limited supply of donor organs. Recent strategies to combat this problem have focused on judicious listing, maximal utilization of available donor organs, and safely extending the lives of patients on the waitlist. New demands on the organ supply chain will continue to stress the system, making these efforts of the highest importance.Clinical Trial Registry Number not applicable.

Impact of Race on Listing and Waitlist Mortality in Pediatric Cardiac Transplantation

PurposeSocial 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.MethodsData 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.ResultsOf 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).ConclusionBlack 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. 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.

False Positive Hepatitis C Virus Serologies in Pediatric Patients with Left Ventricular Assist Devices

Introduction Left ventricular assist devices (LVAD) are being used more frequently in pediatric patients with advanced heart failure as a bridge to transplant. Pediatric centers began implanting the HeartMate 3 LVAD in 2017 and it has become the LVAD of choice at many centers, including our own. Allosensitization is commonly observed after LVAD placement, resulting in higher frequencies of auto-antibodies, though the pathophysiology of this phenomenon is not well understood. Viral hepatitis screening is done prior to transplant, but there are no current guidelines on type of testing and timing with regards to LVAD placement. Case Report Three pediatric patients, aged 7-12 years old, each received an LVAD as bridge to orthoptic heart transplant (OHT) between May 2019 - September 2020. All were otherwise healthy and had negative hepatitis C (HCV) antibody tests prior to Heartmate 3 LVAD placement as part of the pre-transplant infectious work up. Repeat HCV serologic testing obtained shortly before cardiac transplant were positive in all three patients. The patients had no signs or symptoms of acute HCV infection, received infrequent blood transfusions between LVAD placement and OHT, and had no increased risk behaviors. Concurrent HCV quantitative PCR testing was done in two patients and both were negative. HCV antibody testing repeated within six weeks from LVA removal was negative in all three patients. Summary False positive HCV serology secondary to immunogenicity of LVADs has been described in adult literature. Our case series is the first, to our knowledge, to be described in pediatric patients. Adult data suggests that the false positive HCV serology can occur in 16-59% of cohorts post-LVAD. This is thought to be due to immunogenicity of the LVAD as serologies revert after the LVAD is explanted. Our experience demonstrates the importance of standardizing HCV testing in patients both pre- and post-LVAD as a bridge to OHT. Furthermore, acquisition of hepatitis C infection is rare in children and pediatric cardiac transplant providers should be aware of the possibility of false positive HCV antibody tests in this clinical scenario and the importance of confirmatory testing with quantitative PCR if concerned.

Implementation of defined criteria for clinical pharmacists in a pediatric cardiac transplant ambulatory clinic

AbstractIntroductionThe United Network of Organ Sharing (UNOS) bylaws and Centers for Medicare and Medicaid Services (CMS) accreditation standards require that transplant centers have a pharmacist. However, there are no established guidelines and there is a paucity of literature describing pharmacists in the pediatric ambulatory setting.ObjectiveThis project aims to describe the activities of pediatric clinical pharmacists in an ambulatory pediatric cardiac transplant clinic.MethodsThis is a single‐center pilot project describing pediatric clinical pharmacist interventions before (phase I) and after (phase II) implementation of comprehensive and standardized clinical activities. The list of defined key clinical activities was developed using UNOS and CMS accreditation standards, an evaluation of the literature, and cardiac transplant team feedback.ResultsPrior to a defined list of clinical activities, pediatric clinical pharmacists saw 74 unique patients during 174 patient encounters and recorded 240 interventions (phase I). Following implementation of standard activities, pediatric clinical pharmacists saw 81 unique patients during 225 patient encounters and recorded 510 interventions (phase II). The development of defined key activities led to a 129.4% increase in documented interventions per patient encounter. Interventions with the greatest increase included: medication schedule (phase I, 13.2%; phase II, 37.3%; P &lt; .001), medication dose adjustment (phase I, 5.7%; phase II, 22.2%; P &lt; .001), outpatient pharmacy coordination (phase I, 1.1%; phase II, 15.6%; P &lt; .001), medication discontinuation (phase I, 0.6%; phase II, 9.3%; P &lt; .001), and medication adherence education (phase I, 0%; phase II, 6.2%; P &lt; .001).ConclusionThere was a significant increase in the number and variety of medication‐related interventions after the development and implementation of defined key clinical activities for pediatric clinical pharmacists in a pediatric cardiac transplant ambulatory care clinic.