Review on clinician bias and its impact on racial and socioeconomic disparities in pediatric heart transplantation.

This expert review seeks to highlight implicit bias in health care, transplant medicine, and pediatric heart transplantation to focus attention on the role these biases may play in the racial/ethnic and socioeconomic disparities noted in pediatric heart transplantation. This review breaks down the transplant decision making process to highlight points at which implicit bias may affect outcomes and discuss how the science of human decision making may help understand these complex processes.

Using machine learning to predict five-year transplant-free survival among infants with hypoplastic left heart syndrome.

Hypoplastic left heart syndrome (HLHS) is a congenital malformation commonly treated with palliative surgery and is associated with significant morbidity and mortality. Risk stratification models have often relied upon traditional survival analyses or outcomes data failing to extend beyond infancy. Individualized prediction of transplant-free survival (TFS) employing machine learning (ML) based analyses of outcomes beyond infancy may provide further valuable insight for families and healthcare providers along the course of a staged palliation. Data from both the Pediatric Heart Network (PHN) Single Ventricle Reconstruction (SVR) trial and Extension study (SVR II), which extended cohort follow up for five years was used to develop ML-driven models predicting TFS. Models incrementally incorporated features corresponding to successive phases of care, from pre-Stage 1 palliation (S1P) through the stage 2 palliation (S2P) hospitalization. Models trained with features from Pre-S1P, S1P operation, and S1P hospitalization all demonstrated time-dependent area under the curves (td-AUC) beyond 0.70 through 5 years following S1P, with a model incorporating features through S1P hospitalization demonstrating particularly robust performance (td-AUC 0.838 (95% CI 0.836-0.840)). Machine learning may offer a clinically useful alternative means of providing individualized survival probability predictions, years following the staged surgical palliation of hypoplastic left heart syndrome.

Three decades of collaboration through the Pediatric Heart Transplant Society Registry: A journey through registry data with a highlight on children with single ventricle anatomy.

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.

Lymphatic Leakage in Pediatric Heart Transplantation: Early Recognition and Timely Management with Interventional Radiologic and Endoscopic Therapy.

Protein-losing enteropathy (PLE) is a severe complication of the Fontan procedure that leads to systemic complications owing to enteric protein loss. Hepatoduodenal lymphatic leakage resulting from increased lymphatic pressure is one such complication. We present the case of a pediatric heart transplant patient who experienced refractory PLE symptoms requiring serial albumin infusions and exhibited lymphatic leakage into the duodenum. Using diagnostic lymphangiography and endoscopy, we identified the affected area and treated it successfully with endoscopic sclerotherapy using ethanolamine injection. This treatment allowed for the cessation of lymphatic fluid and may serve as a potential intervention for PLE-associated hepatoduodenal lymphatic leakage. The present case highlights the importance of early recognition and timely intervention with radiology and endoscopic therapy to manage PLE and its associated complications.

Risk factors for 1-year allograft loss in pediatric heart transplant patients using machine learning: An analysis of the pediatric heart transplant society database.

BACKGROUND: Pediatric heart transplant patients are at greatest risk of allograft loss in the first year. We assessed whether machine learning could improve 1-year risk assessment using the Pediatric Heart Transplant Society database. METHODS: Patients transplanted from 2010 to 2019 were included. The primary outcome was 1-year graft loss free survival. We developed a prediction model using cross-validation, by comparing Cox regression, gradient boosting, and random forests. The modeling strategy with the best discrimination and calibration was applied to fit a final prediction model. We used Shapley additive explanation (SHAP) values to perform variable selection and to estimate effect sizes and importance of individual variables when interpreting the final prediction model. RESULTS: Cumulative incidence of graft loss or mortality was 7.6%. Random forests had favorable discrimination and calibration compared to Cox proportional hazards with a C-statistic (95% confidence interval [CI]) of 0.74 (0.72, 0.76) versus 0.71 (0.69, 0.73), and closer alignment between predicted and observed risk. SHAP values computed using the final prediction model indicated that the diagnosis of congenital heart disease (CHD) increased 1 year predicted risk of graft loss by 1.7 (i.e., from 7.6% to 9.3%), need for mechanical circulatory support increased predicted risk by 2, and single ventricle CHD increased predicted risk by 1.9. These three predictors, respectively, were also estimated to be the most important among the 15 predictors in the final model. CONCLUSIONS: Risk prediction models used to facilitate patient selection for pediatric heart transplant can be improved without loss of interpretability using machine learning.

Survival analysis for pediatric heart transplant patients using a novel machine learning algorithm: A UNOS analysis.

BACKGROUND: Impact of pretransplantation risk factors on mortality in the first year after heart transplantation remains largely unknown. Using machine learning algorithms, we selected clinically relevant identifiers that could predict 1-year mortality after pediatric heart transplantation. METHODS: Data were obtained from the United Network for Organ Sharing Database for years 2010-2020 for patients 0-17 years receiving their first heart transplant (N = 4150). Features were selected using subject experts and literature review. Scikit-Learn, Scikit-Survival, and Tensorflow were used. A train:test split of 70:30 was used. N-repeated k-fold validation was performed (N = 5, k = 5). Seven models were tested, Hyperparameter tuning performed using Bayesian optimization and the concordance index (C-index) was used for model assessment. RESULTS: A C-index above 0.6 for test data was considered acceptable for survival analysis models. C-indices obtained were 0.60 (Cox proportional hazards), 0.61 (Cox with elastic net), 0.64 (gradient boosting), 0.64 (support vector machine), 0.68 (random forest), 0.66 (component gradient boosting), and 0.54 (survival trees). Machine learning models show an improvement over the traditional Cox proportional hazards model, with random forest performing the best on the test set. Analysis of the feature importance for the gradient boosted model found that the top 5 features were the most recent serum total bilirubin, the travel distance from the transplant center, the patient body mass index, the deceased donor terminal Serum glutamic pyruvic transaminase/Alanine transaminase (SGPT/ALT), and the donor PCO2. CONCLUSIONS: Combination of machine learning and expert-based methodology of selecting predictors of survival for pediatric heart transplantation provides a reasonable prediction of 1- and 3-year survival outcomes. SHapley Additive exPlanations can be an effective tool for modeling and visualizing nonlinear interactions.

Diagnostic and management roles of FDG PET/CT imaging in post-transplant lympho-proliferation in pediatric heart transplantation.

BACKGROUND: Post-transplant lymphoproliferative disorder (PTLD) is a serious complication of pediatric heart transplant (PHTx). 18F-FDG PET/CT has been used to differentiate early lympho-proliferation from more advanced PTLD. We report our experience with PET/CT in the management of PTLD following PHTx. METHODS: This was a retrospective study of 100 consecutive PHTx recipients at our institution between 2004 and 2018. Patients who underwent PET/CT or conventional CT scans to evaluate for PTLD or high Epstein-Barr viral load were included. RESULTS: Males, eight females. Median age at transplant was 3.5 months (IQR = 1.5-27.5). Median age at PTLD diagnosis was 13.3 years (IQR = 9.2-16.1). Median time between transplant and PTLD diagnosis was 9.5 (IQR = 4.5-15) years. Induction agents were used in 12 patients (50%): Thymoglobulin (N = 9), anti-IL2 (N = 2), and Rituximab (N = 1). Eighteen patients (75%) had PET/CT, of whom 14 had 18FDG-avid PTLD. Six had conventional CT. Nineteen patients (79.2%) had diagnostic biopsy confirmation of PTLD, and 5 (20.8%) had excisional biopsies. Two patients had Hodgkin's lymphoma; nine had monomorphic PTLD; eight had polymorphic PTLD; five were classified as other. Nine patients had monomorphic PTLD, including seven with diffuse large cell lymphoma (DLBC) and one with T cell lymphoma. The majority (16/24) had multi-site involvement at PTLD diagnosis, and PET/CT showed that 31.3% (5/16) had easily accessible subcutaneous nodes. Seventeen patients (overall survival 71%) underwent successful treatment without recurrence of PTLD. Of seven deaths (7/24, 29%), five had DLBC lymphoma, one had polymorphic PTLD and one had T-cell lymphoma. CONCLUSION: PET-CT allowed simultaneous anatomical and functional assessment of PTLD lesions, while guiding biopsy. In patients with multiple lesions, PET/CT revealed the most prominent and active lesions, improving diagnostic accuracy.

Race and Socioeconomic Bias in Pediatric Cardiac Transplantation.

BACKGROUND: To date, no studies evaluated implicit bias among clinicians caring for children with advanced heart failure. OBJECTIVES: This study aims to evaluate implicit racial and socioeconomic bias among pediatric heart transplant clinicians. METHODS: A 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. RESULTS: Of 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). CONCLUSIONS: As 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.

Optimal Donor Allograft Function: The Search for the Lowest Acceptable Donor Left Ventricular Ejection Fraction in Pediatric Heart Transplantation.

BACKGROUND: The availability of heart donors is limited by organ shortage. Due to concerns of reduced survival, donors with depressed left ventricular ejection fraction (LVEF <50%) have been cautiously used in pediatric heart transplantation. One strategy to expand the donor pool is to re-evaluate whether lower donor LVEF may be acceptable for transplantation. METHODS: We performed a multicenter retrospective cohort study of patients <18 y receiving heart transplants from April 2007 to September 2021 using the United Network of Organ Sharing dataset. We excluded retransplants and multiorgan transplants. Cut-point analyses of LVEF was performed and Kaplan-Meier method was used to compare 1-y survival for new cut-points and the standard (LVEF >50%). RESULTS: The analytic sample consisted of 5255 patients. Recipients receiving hearts with lower LVEFs were more likely to be on ventilator and extracorporeal membrane oxygenation support. Recipients did not differ in waitlist times or transplant status. Cut-point analysis identified LVEF 45% as a potentially new cutoff. One-year survival of recipients of donors with LVEF ≥45% (92.1%; 95% confidence interval [CI], 91.3%-92.8%) was similar to that of LVEF >50% (92.1%; CI, 91.4%-92.9%). Survival for the LVEF 45%-49% (88.8%; CI, 72.9%-95.7%) cohort was slightly lower than the ≥50% cohort, albeit nonsignificant. CONCLUSIONS: One-year survival among pediatric heart transplants using a donor heart LVEF threshold of 45% or 40% was similar to a threshold of 50%. However, the finding is based on a small number of patients with LVEF <50%, and future larger prospective studies are warranted to confirm the findings of this study before a lower LVEF threshold is considered.

Basiliximab therapy for immune-mediated bowel disease in a pediatric heart transplant patient.

In pediatric patients who undergo heart transplantation, severe immune-mediated bowel disease has been reported. Management is complex, and there are little data discussing the use of basiliximab for immune-mediated bowel disease. This case report discusses a pediatric patient who developed immune-mediated bowel disease following heart transplantation and was successfully managed with basiliximab.

Prolonged hospital length of stay after pediatric heart transplantation: A machine learning and logistic regression predictive model from the Pediatric Heart Transplant Society.

BACKGROUND: Heart transplantation (HT) is the gold standard for managing end-stage heart failure. Multiple quality metrics, including length of stay (LOS), have been used in solid organ transplantation. However, limited data are available regarding trends and factors influencing LOS after pediatric HT. We hypothesized that various donor, peri-transplant and recipient factors affect LOS after pediatric HT. METHODS: We analyzed patients <18years at time of HT from January 2005 to December 2018 in the Pediatric Heart Transplant Society database, and examined LOS trends, defined prolonged LOS (PLOS = LOS>30days after HT), identified factors associated with PLOS and assessed outcomes. RESULTS: Of 4827 patients undergoing HT, 4414 patients were discharged and included for analysis. Overall median LOS was 19days[13,34]. Median LOS was longer in patients with congenital heart disease(CHD = 25days[15,43] than with cardiomyopathy(CM = 17days[12,27] across all ages. Median LOS in age <1year was 26-days[16,45.5] and in age >10year was 16days[11,26]. PLOS was seen in 1313 patients(30%). Patients with PLOS were younger, smaller and had longer CPB times. There was no difference in utilization of VAD at HT between groups, however, ECMO use at listing(8.45% vs 2.93%,p < 0.05) and HT was higher in the PLOS group(9.22% vs 1.58%,p < 0.05). PLOS was more common in patients with previous surgery, CHD, single ventricle physiology, recipient history of cardiac arrest or CPR, end organ dysfunction, lower GFR, use of mechanical ventilation at HT and Status 1A at HT. CONCLUSION: We present novel findings of LOS distribution and define PLOS after pediatric HT, providing a quality metric for individual programs to utilize and study in their practice.

Impact of Coronavirus-2019 On Pediatric and Adult Heart Transplantation Waitlist Activity and Mortality in The United States: A Descriptive Approach.

BACKGROUND: Transplant centers saw a substantial reduction in deceased donor solid organ transplantation since the beginning of the coronavirus 2019 (COVID-19) pandemic in the United States. There is limited data on the impact of COVID-19 on adult and pediatric heart transplant volume and variation in transplant practices. We hypothesized that heart transplant activity decreased during COVID-19 with associated increased waitlist mortality. METHODS: The United Network for Organ Sharing (UNOS) database was used to identify patients at the time of listing for heart transplant from 2017-2020. Patients were categorized as pediatric (<18 years) or adult (≥18 years) and as pre-COVID (2017-2019) or post-COVID (2020). Regional and statewide data were taken from United States Census Bureau. CovidActNow project was used to obtain COVID-19 mortality rates. FINDINGS: Among pediatric patients, average time on the waiting list decreased by 28 days. Even though the average number of pediatric transplants (n=39 per month) did not change significantly during 2020, there was a temporal decline in the first quarter of 2020 followed by a sharp increase. Overall absolute pediatric waitlist mortality decreased from 5•31 to 4•73, however female mortality increased by 2%. Regional differences in pediatric mortality were observed: Northeast, decreased by 7•5%; Midwest, decreased by 9%; West, increased by 3•5%; and South, increased by 13%. North Dakota (0•55), Oklahoma (0•21) and Hawaii (0•33) showed higher mortality than other states per 100,000. In adults, average time on waiting list increased by 40 days and there was an increase in the number of transplants from 242 to 266. Adult waitlist mortality had a larger decrease, 18•44 to 15•70, with an increase in female mortality of 7%. Regional differences in adult mortality were also observed: Northeast, decreased by 3%; Midwest, increased by 5•5%; West, increased by 4•5% and South, decreased by 5%. Iowa (0•37), Wyoming (0•22), Arkansas (0•18) and Vermont (0•19) had the highest mortality per 100,000 compared to the other states. INTERPRETATION: Pediatric heart transplant volume declined in early 2020 followed by a later increase, while adult transplant volume increased all year round. Although, overall pediatric waitlist mortality decreased, female waitlist mortality increased for both adults and pediatrics. Regional differences in waitlist mortality were observed for both pediatrics and adults. Future studies are needed to understand this initial correlation and to determine the impact of COVID-19 on heart transplant recipients. FUNDING: This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

Expanded utilization of rituximab in paediatric cardiac transplant patients.

WHAT IS KNOWN AND OBJECTIVE: Epstein-Barr virus (EBV) viraemia and autoimmune cytopenias (AICs) are significant complications that occur following paediatric solid organ transplantation. A variety of treatment methods have been investigated but limited research has focused on the utilization of rituximab in paediatric cardiac transplant recipients for these indications. Rituximab is a monoclonal antibody that binds the CD20 antigen on the surface of B-type lymphocytes resulting in B-cell cytotoxicity. It is considered a second-line therapy for treatment of autoimmune cytopenias and EBV viraemia following adult solid organ transplant (SOT) and haematopoietic stem cell transplant (HSCT). However, data for its use in the paediatric population for treatment of autoimmune cytopenias are lacking. Dosing is based on adult studies, and the frequency and length of therapy associated with resolution of EVB viraemia and AICs in paediatric cardiac transplant recipients is unknown. The objective of this retrospective study was to describe the dosing and length of therapy of expanded off-label use of rituximab for the management of refractory EBV viraemia and AICs, specifically in paediatric cardiac transplant patients. METHODS: A retrospective chart review was conducted evaluating children <18 years of age who underwent cardiac transplantation, were diagnosed with EBV viraemia or autoimmune cytopenia, and subsequently received treatment with rituximab between June 1995 and October 2018. Data were analysed descriptively. RESULTS AND DISCUSSION: Of all (n = 188) paediatric cardiac transplant recipients since 1995, 10 patients met the inclusion/exclusion criteria. Primary diagnoses were EBV viraemia (n = 6), immune haemolytic anaemia (n = 3) and immune thrombocytopenic purpura (n = 1). Complete responses were observed in 83.3% and 100% of patients with EVB viraemia and AICs treated with rituximab, respectively. All patients (n = 10) received rituximab 325 mg/m2 at weekly intervals. The number of total doses associated with complete resolution was 4-6 doses for EBV viraemia and 2-4 doses for AICs. The most common adverse events reported were neutropenia (n = 3), thrombocytopenia (n = 4), infusion reactions (n = 1) and significant anaemia (n = 2). WHAT IS NEW AND CONCLUSION: Although the efficacy of rituximab for treatment of EBV viraemia and autoimmune cytopenia in the paediatric cardiac transplant population remains unclear, our study supported the benefit of rituximab when added to therapy for treatment of EBV viraemia and ACIs.

Heart Transplantation for Pediatric and Congenital Cardiac Disease: A Comparison of Two Eras over 23 Years and 188 Transplants at a Single Institution.

BACKGROUND: To assess changes in patterns of practice and outcomes over time, we reviewed all patients who underwent heart transplantation (HTx) at our institution and compared two consecutive eras with significantly different immunosuppressive protocols (cohort 1 [80 HTx, June 1995-June 2006]; cohort 2 [108 HTx, July 2006-September 2018]). METHODS: Retrospective study of 180 patients undergoing 188 HTx (June 1995-September 2018; 176 first time HTx, 10 second HTx, and 2 third HTx). In 2006, we commenced pre-HTx desensitization for highly sensitized patients and started using tacrolimus as our primary postoperative immunosuppressive agent. The primary outcome was mortality. Survival was modeled by the Kaplan-Meier method. Univariable and multivariable Cox proportional hazard models were created to identify prognostic factors for survival. RESULTS: Our 188 HTx included 18 neonates, 85 infants, 83 children, and 2 adults (>18 years). Median age was 260.0 days (range: 5 days-23.8 years). Median weight was 7.5 kg (range: 2.2-113 kg). Patients in cohort 1 were less likely to have been immunosensitized preoperatively (12.5% vs 28.7%, P = .017). Nevertheless, Kaplan-Meier analysis suggested superior survival in cohort 2 (P = .0045). Patients in cohort 2 were more likely to be alive one year, five years, and ten years after HTx. Multivariable analysis identified the earlier era (hazard ratio [HR] [95% confidence interval] for recent era = 0.32 [0.14-0.73]), transplantation after prior Norwood operation (HR = 4.44 [1.46-13.46]), and number of prior cardiac operations (HR = 1.33 [1.03-1.71]) as risk factors for mortality. CONCLUSIONS: Our analysis of 23 years of pediatric and congenital HTx reveals superior survival in the most recent 12-year era, despite the higher proportion of patients with elevated panel reactive antibody in the most recent era. This improvement was temporally associated with changes in our immunosuppressive strategy.

Survival After Heart Transplant Listing for Infants on Mechanical Circulatory Support.

Background Infants with heart failure remain at significant risk for wait list mortality, despite mechanical circulatory support (MCS). It is unclear if the outcomes are influenced by modality of support or underlying diagnosis. We sought to compare the outcomes of infants <10 kg, focusing on modality of support and underlying diagnosis. Methods and Results Using the Pediatric Heart Transplant Society database, we evaluated survival following first MCS device in children <10 kg who were listed for heart transplant between 2010 and 2018. There were 2049 children <10 kg, with the predominant diagnosis being congenital heart disease (CHD) (59.8% [n=1226]) and 28.1% (n=577) requiring MCS. Extracorporeal membrane oxygenation (ECMO) was the most common form of MCS at listing, with ventricular assist device (VAD) more common after listing. There was no difference in the use of ECMO at or after listing for cardiomyopathy versus CHD (8.9% versus 7.2%; P=0.2; 5.4% versus 6.4%; P=0.4). However, there was a significant difference in the use of VAD both at listing (8% versus 2.4%; P<0.001) and after (22.8% versus 5.1%; P<0.001) between the 2 groups. When comparing these groups, patients with CHD were smaller and younger and had a higher proportion with previous cardiac surgery. Survival at 3 months demonstrated better survival for VAD therapy compared with ECMO (74.3% versus 48.6%; P<0.001). In patients <5 kg, survival did not differ between ECMO and VAD (P=0.01) for the CHD or the cardiomyopathy group (P=0.38), but patients with cardiomyopathy demonstrated better survival on both forms of support. Conclusions Survival for patients <10 kg on ECMO is inferior compared with VAD. Patients with cardiomyopathy <5 kg had better survival with both modes of MCS compared with those with CHD. These findings support the need for small, durable devices for neonates and infants, with particular focus in patients with CHD.

Hyaluronidase-Facilitated High-Dose Subcutaneous IgG Effectively Controls Parvovirus B19 Infection in a Pediatric Cardiac Transplant Patient With Severe T-Cell Lymphopenia.

We treated three pediatric cardiac transplant patients with chronic parvovirus viremia with high-dose intravenous immunoglobulin (HD-IVIG). One patient with severe T-cell lymphopenia suffered recurrent viremia and aseptic meningitis, which resolved remarkably when he was switched to high-dose hyaluronidase-facilitated subcutaneous immunoglobulin (HD-SCIG-Hy). We discuss the advantages of HD-SCIG-Hy vs HD-IVIG treatment for similar cases.

Resource utilization of cytomegalovirus immune globulin in prevention and treatment of cytomegalovirus infection in pediatric heart transplantation.

BACKGROUND: There is debate whether cytomegalovirus immunoglobulin (CMV-Ig) is also needed for CMV prevention in heart transplant recipients in the era of good anti-viral drugs. METHODS: We conducted a cost-savings quality initiative on CMV-Ig eventually leading to discontinuation of routine use of CMV-Ig for CMV prevention. Subsequently, a retrospective cohort study was conducted, comparing patients in cohort I (CMV-Ig plus anti-viral drugs, 2013-2015) to cohort II (anti-virals alone, 2015-2017). The medication acquisition costs and outcomes of CMV infection were assessed. RESULTS: There were 39 total patients: 22/39(56%) in cohort I, with mean follow-up of 35.14 ± 17.38 months and 17/39(44%) in cohort II, mean follow-up of 19.12 ± 7.08 months. In cohort I, 5/22(22.7%) patients died from causes unrelated to CMV and 0/17 in cohort II died. There were 5/22(22.7%) patients in cohort I, and 2/17(9%) patients in cohort II that developed CMV infection (P = .508). Freedom from rejection was 81.8% (18/22) in cohort I, and 71% (12/17) in cohort II (P = .46), and 100% for allograft vasculopathy. There was significant reduction in medication acquisition cost following the protocol change of $260 839 or $15 343 per patient. CONCLUSION: Our study demonstrated an acquisition cost savings with similar clinical outcomes utilizing anti-viral CMV prophylaxis alone vs anti-viral prophylaxis plus CMV-Ig.

Cardiomyopathy in Children: Classification and Diagnosis: A Scientific Statement From the American Heart Association.

In this scientific statement from the American Heart Association, experts in the field of cardiomyopathy (heart muscle disease) in children address 2 issues: the most current understanding of the causes of cardiomyopathy in children and the optimal approaches to diagnosis cardiomyopathy in children. Cardiomyopathies result in some of the worst pediatric cardiology outcomes; nearly 40% of children who present with symptomatic cardiomyopathy undergo a heart transplantation or die within the first 2 years after diagnosis. The percentage of children with cardiomyopathy who underwent a heart transplantation has not declined over the past 10 years, and cardiomyopathy remains the leading cause of transplantation for children >1 year of age. Studies from the National Heart, Lung, and Blood Institute-funded Pediatric Cardiomyopathy Registry have shown that causes are established in very few children with cardiomyopathy, yet genetic causes are likely to be present in most. The incidence of pediatric cardiomyopathy is ≈1 per 100 000 children. This is comparable to the incidence of such childhood cancers as lymphoma, Wilms tumor, and neuroblastoma. However, the published research and scientific conferences focused on pediatric cardiomyopathy are sparcer than for those cancers. The aim of the statement is to focus on the diagnosis and classification of cardiomyopathy. We anticipate that this report will help shape the future research priorities in this set of diseases to achieve earlier diagnosis, improved clinical outcomes, and better quality of life for these children and their families.