Waitlist Outcomes for Pediatric Heart Transplantation in the Current Era: An Analysis of the Pediatric Heart Transplant Society Database.

BACKGROUND: Waitlist mortality (WM) remains elevated in pediatric heart transplantation. Allocation policy is a potential tool to help improve WM. This study aims to identify patients at highest risk for WM to potentially inform future allocation policy changes. METHODS: The Pediatric Heart Transplant Society database was queried for patients <18 years of age indicated for heart transplantation between January 1, 2010 to December 31, 2021. Waitlist mortality was defined as death while awaiting transplant or removal from the waitlist due to clinical deterioration. Because WM is low after the first year, analysis was limited to the first 12 months on the heart transplant list. Kaplan-Meier analysis and log-rank testing was conducted to compare unadjusted survival between groups. Cox proportional hazard models were created to determine risk factors for WM. Subgroup analysis was performed for status 1A patients based on body surface area (BSA) at time of listing, cardiac diagnosis, and presence of mechanical circulatory support. RESULTS: In total 5974 children met study criteria of which 3928 were status 1A, 1012 were status 1B, 963 were listed status 2, and 65 were listed status 7. Because of the significant burden of WM experienced by 1A patients, further analysis was performed in only patients indicated as 1A. Within that group of patients, those with smaller size and lower eGFR had higher WM, whereas those patients without congenital heart disease or support from a ventricular assist device (VAD) at time of listing had decreased WM. In the smallest size cohort, cardiac diagnoses other than dilated cardiomyopathy were risk factors for WM. Previous cardiac surgery was a risk factor in the 0.3 to 0.7 m2 and >0.7 m2 BSA groups. VAD support was associated with lower WM other than in the single ventricle cohort, where VAD was associated with higher WM. Extracorporeal membrane oxygenation and mechanical ventilation were associated with increased risk of WM in all cohorts. CONCLUSIONS: There is significant variability in WM among status-1A patients. Potential refinements to current allocation system should factor in the increased WM risk we identified in patients supported by extracorporeal membrane oxygenation or mechanical ventilation, single ventricle congenital heart disease on VAD support and small children with congenital heart disease, restrictive cardiomyopathy, or hypertrophic cardiomyopathy.

Changing Strategy Between Bridge to Transplant and Destination LVAD Therapy After the First 3 Months: Analysis of the STS-INTERMACS Database.

BACKGROUND: Left ventricular assist devices (LVADs) have been implanted as bridge to transplantation (BTT), bridge to candidacy (BTC) or destination therapy (DT) on the basis of relative and absolute contraindications to transplantation. Multiple factors may lead to changes in the strategy of support after LVAD implantation. METHODS: Based on INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) 2012-2020 data, 11,262 patients survived to 3 months on continuous-flow LVADs with intent of BTT or DT. Preimplant characteristics and early events post-LVAD were analyzed in relation to changes in BTT or DT strategy during the next 12 months. RESULTS: Among 3216 BTT patients at 3 months, later transplant delisting or death without transplant occurred in 536 (16.7%) and was more common with age, profiles 1-2, renal dysfunction, and independently for prior cardiac surgery (HR 1.25, 95% CI 1.04-1.51; P = 0.02). Post-LVAD events of infections, gastrointestinal bleeding, stroke, and right heart failure as defined by inotropic therapy, predicted delisting and death, as did in-hospital location at 3 months (HR 1.67, 95% CI 1.20-2.33; P = 0.0024). Of 8046 patients surviving to 3 months with the intent of destination therapy, 750 (9.3%) subsequently underwent listing or transplantation, often with initial histories of acute HF (HR 1.70, 95% CI 1.27-2.27; P = 0.0012) or malnutrition-cachexia (1.73, 95% CI 1.14-2.63; P = 0.0099). Multiple gastrointestinal bleeding events (≥ 4) with LVAD increased transition from BTT to DT (HR 4.22, 95% CI 1.46-12.275; P = 0.0078) but also from DT to BTT (HR 5.17, 95% CI 1.92-13.9; P = 0.0011). CONCLUSIONS: Implant strategies change over time in relation to preimplant characteristics and adverse events post implant. Preimplant recognition of factors predicting later change in implant strategy will refine initial triage, whereas further reduction of post-LVAD complications will expand options, including eventual consideration of heart transplantation.

Social Determinants of Health and Outcomes After Pediatric Ventricular Assist Device Implantation.

BACKGROUND: Limited research exists on the influence of social determinants of health (SDOH) on outcomes in pediatric patients with advanced heart failure receiving mechanical circulatory support. METHODS: Linkage of the Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs) and Society of Thoracic Surgeon's Congenital Heart Surgery Database (STS-CHSD) identified pediatric patients who underwent ventricular assist device (VAD) implantation from 2012 to 2022 with available residential zip codes. Utilizing the available zip codes, each patient was assigned a Childhood Opportunity Index (COI) score. Level of childhood opportunity, race, and insurance type were used as proxies for SDOH. Major outcomes included death, transplant, alive with device, and recovery. Secondary outcomes were adverse events. Statistical analyses were performed using the Kaplan-Meier survival, competing risk analyses, and multivariable Cox proportional hazards model. RESULTS: Three hundred seventeen patients were included in the study. Childhood opportunity level and insurance status did not significantly impact morbidity or mortality after VAD implantation. White race was associated with reduced 1-year survival (71% in White vs. 87% in non-White patients, p = 0.05) and increased risk of pump thrombosis (p = 0.02). CONCLUSION: Childhood opportunity level and insurance status were not linked to morbidity and mortality in pediatric patients after VAD implantation. Notably, White race was associated with higher mortality rates. The study underscores the importance of considering SDOH in evaluating advanced therapies for pediatric heart failure and emphasizes the need for accurate socioeconomic data collection in future studies and national registries.

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.

PROMIS: Physical, Mental and Social Health Outcomes Improve From Before to Early After LVAD Implant: Findings From the Mechanical Circulatory Support: Measures of Adjustment and Quality of Life (MCS A-QOL) Study.

Study participants (n = 272) completed 12 Patient-Reported Outcomes Measurement Information System (PROMIS) physical, mental and social health measures (questionnaires) prior to implantation of a left ventricular assist device (LVAD) and again at 3 and 6 months postimplant. All but 1 PROMIS measure demonstrated significant improvement from pre-implant to 3 months; there was little change between 3 and 6 months. Because PROMIS measures were developed in the general population, patients with an LVAD, their caregivers and their clinicians can interpret the meaning of PROMIS scores in relation to the general population, helping them to monitor a return to normalcy in everyday life.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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.

The Fontan immunophenotype and post-transplant outcomes in children: A multi-institutional study.

BACKGROUND: Patients after Fontan palliation represent a growing pediatric population requiring heart transplant (HTx) and often have lymphopenia (L) and/or hypogammaglobinemia that may be exacerbated by protein-losing enteropathy (PLE, P). The post-HTx effects of this altered immune phenotype are not well studied. METHODS: In this study of the Pediatric Heart Transplant Society Registry, 106 Fontan patients who underwent HTx between 2005 and 2018 were analyzed. The impact of lymphopenia and PLE on graft survival, infection, rejection, and malignancy was analyzed at 1 and 5 years post-HTx. RESULTS: The following combinations of lymphopenia and PLE were noted: +L+P, n = 37; +L-P, n = 23; -L+P, n = 10; and -L-P, n = 36. Graft survival between the groups was similar within the first year after transplant (+L+P: 86%, +L-P: 86%, -L+P: 87%, -L-P: 89%, p = .9). Freedom from first infection post-HTx was greatest among -L-P patients compared to patients with either PLE, lymphopenia, or both; with a 22.1% infection incidence in the -L-P group and 41.4% in all others. These patients had a significantly lower infection rate in the first year after HTx (+L+P: 1.03, +L-P: 1, -L+P: 1.3, -L-P: 0.3 infections/year, p < .001) and were similar to a non-single ventricle CHD control group (0.4 infections/year). Neither freedom from rejection nor freedom from malignancy 1 and 5 years post-HTx, differed among the groups. CONCLUSIONS: Fontan patients with altered immunophenotype, with lymphopenia and/or PLE, are at increased risk of infection post-HTx, although have similar early survival and freedom from rejection and malignancy. These data may encourage alternative immunosuppression strategies and enhanced monitoring for this growing subset of patients.

Loss of pulsatility with continuous-flow left ventricular assist devices and the significance of the arterial endothelium in von-Willebrand factor production and degradation.

BACKGROUND: Patients on continuous flow ventricular assist devices (CF-VADs) are at high risk for the development of Acquired von-Willebrand Syndrome (AVWS) and non-surgical bleeding. von Willebrand Factor (vWF) plays an essential role in maintaining hemostasis via platelet binding to the damaged endothelium to facilitate coagulation. In CF-VAD patients, degradation of vWF into low MW multimers that are inefficient in facilitating coagulation occurs and has been primarily attributed to the supraphysiological shear stress associated with the CF-VAD impeller. METHODS: In this review, we evaluate information from the literature regarding the unraveling behavior of surface-immobilized vWF under pulsatile and continuous flow pertaining to: (A) the process of arterial endothelial vWF production and release into circulation, (B) the critical shear stress required to unravel surface bound versus soluble vWF which leads to degradation, and (C) the role of pulsatility in on the production and degradation of vWF. RESULTS AND CONCLUSION: Taken together, these data suggests that the loss of pulsatility and its impact on arterial endothelial cells plays an important role in the production, release, unraveling, and proteolytic degradation of vWF into low MW multimers, contributing to the development of AVWS. Restoration of pulsatility can potentially mitigate this issue by preventing AVWS and minimizing the risk of non-surgical bleeding.

TGA + IVS + LVOTO: patterns of practice and outcomes.

PURPOSE: Transposition of great arteries with intact ventricular septum and left ventricular outflow tract obstruction (TGA + IVS + LVOTO) is uncommon. We reviewed operations performed in patients with TGA + IVS + LVOTO in the European Congenital Heart Surgeons Association Congenital Database (ECHSA-CD). METHODS: All 109 patients with a diagnosis of TGA + IVS + LVOTO in ECHSA-CD who underwent cardiac surgery during a 21-year period (01/2000-02/2021, inclusive) were included. Preoperative variables, operative data, and postoperative outcomes were collected. RESULTS: These 109 patients underwent 176 operations, including 37 (21.0%) arterial switch operations (ASO), 26 (14.2%) modified Blalock-Taussig-Thomas shunts (MBTTS), 11 (6.2%) Rastelli operations, and 13 (7.3%) other palliative operations (8 superior cavopulmonary anastomosis[es], 4 Fontan, and 1 other palliative procedure). Of 37 patients undergoing ASO, 22 had a concomitant procedure.There were 68 (38.6%) reoperations, including 11 pacemaker procedures and 8 conduit operations. After a systemic-to-pulmonary artery shunt, reoperations included shunt reoperation (n = 4), Rastelli (n = 4), and superior cavopulmonary anastomosis (n = 3).Overall Operative Mortality was 8.2% (9 deaths), including three following ASO, two following "Nikaidoh, Kawashima, or LV-PA conduit" procedures, and two following Rastelli. Postoperative complications occurred after 36 operations (20.4%). The most common complications were delayed sternal closure (n = 11), postoperative respiratory insufficiency requiring mechanical ventilation >7 days (n = 9), and renal failure requiring temporary dialysis (n = 8). CONCLUSION: TGA + IVS + LVOTO is rare (109 patients in ECHSA-CD over 21 years). ASO, MBTTS, and Rastelli are the most common operations performed for TGA + IVS + LVOTO. Larger international studies with long-term follow-up are needed to better define the anatomy of the LVOTO and to determine the optimal surgical strategy.

Advocacy at the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery.

The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery (WCPCCS) will be held in Washington DC, USA, from Saturday, 26 August, 2023 to Friday, 1 September, 2023, inclusive. The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery will be the largest and most comprehensive scientific meeting dedicated to paediatric and congenital cardiac care ever held. At the time of the writing of this manuscript, The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery has 5,037 registered attendees (and rising) from 117 countries, a truly diverse and international faculty of over 925 individuals from 89 countries, over 2,000 individual abstracts and poster presenters from 101 countries, and a Best Abstract Competition featuring 153 oral abstracts from 34 countries. For information about the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery, please visit the following website: [www.WCPCCS2023.org]. The purpose of this manuscript is to review the activities related to global health and advocacy that will occur at the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery.Acknowledging the need for urgent change, we wanted to take the opportunity to bring a common voice to the global community and issue the Washington DC WCPCCS Call to Action on Addressing the Global Burden of Pediatric and Congenital Heart Diseases. A copy of this Washington DC WCPCCS Call to Action is provided in the Appendix of this manuscript. This Washington DC WCPCCS Call to Action is an initiative aimed at increasing awareness of the global burden, promoting the development of sustainable care systems, and improving access to high quality and equitable healthcare for children with heart disease as well as adults with congenital heart disease worldwide.

Cerebrovascular Events in Patients With Centrifugal-Flow Left Ventricular Assist Devices: Propensity Score-Matched Analysis From the Intermacs Registry.

BACKGROUND: Ischemic and hemorrhagic cerebrovascular accidents remain common among patients with centrifugal-flow left ventricular assist devices, despite improvements in survival and device longevity. We compared the incidence of neurologic adverse events (NAEs) associated with 2 contemporary centrifugal-flow left ventricular assist devices: the Abbott HeartMate3 (HM3) and the Medtronic HeartWare HVAD (HVAD). METHODS: Using the Society of Thoracic Surgeons Interagency Registry for Mechanically Assisted Circulatory Support (Intermacs), we collected data on adult patients who received a centrifugal-flow left ventricular assist device as a primary isolated implant between January 1, 2017, and September 30, 2019. Major NAEs were defined as transient ischemic attack, ischemic cerebrovascular accident, or hemorrhagic cerebrovascular accident. The association of HVAD with risk of NAE in the first year after implant was evaluated using propensity score matching to balance for preimplant risk factors. After matching, freedom from first major NAE in the HM3 and HVAD cohorts was compared with Kaplan-Meier curves. A secondary analysis using multivariable multiphase hazard models was used to identify predictors of NAE, which uses a data-driven parametric fit of the early declining and constant phase hazards and the associations of risk factor with either phase. RESULTS: Of 6205 included patients, 3129 (50.4%) received the HM3 and 3076 (49.6%) received the HVAD. Median follow-up was 9 and 12 months (HM3 and HVAD, respectively). Patients receiving HVAD had more major NAEs (16.4% versus 6.4%, P<0.001) as well as each subtype (transient ischemic attack: 3.3% versus 1.0%, P<0.001; ischemic cerebrovascular accident: 7.7% versus 3.4%, P<0.001; hemorrhagic cerebrovascular accident: 7.2% versus 2.0%, P<0.001) than did patients receiving HM3. A propensity-matched cohort balanced for preimplant risk factors showed that HVAD was associated with higher probabilities of major NAEs (% freedom from NAE 82% versus 92%, P<0.001). Device type was not significantly associated with NAEs in the early hazard phase, but HVAD was associated with higher incidence of major NAEs during the constant hazard phase (hazard ratio, 5.71 [CI, 3.90-8.36]). CONCLUSIONS: HM3 is associated with lower hazard of major NAEs than is HVAD beyond the early postimplantation period and during the constant hazard phase. Defining the explanation for this observation will inform device selection for individual patients.

Cerebrovascular Events in Patients With Centrifugal-Flow Left Ventricular Assist Devices: Propensity Score-Matched Analysis From the Intermacs Registry.

BACKGROUND: Ischemic and hemorrhagic cerebrovascular accidents remain common among patients with centrifugal-flow left ventricular assist devices, despite improvements in survival and device longevity. We compared the incidence of neurologic adverse events (NAEs) associated with 2 contemporary centrifugal-flow left ventricular assist devices: the Abbott HeartMate3 (HM3) and the Medtronic HeartWare HVAD (HVAD). METHODS: Using the Society of Thoracic Surgeons Interagency Registry for Mechanically Assisted Circulatory Support (Intermacs), we collected data on adult patients who received a centrifugal-flow left ventricular assist device as a primary isolated implant between January 1, 2017, and September 30, 2019. Major NAEs were defined as transient ischemic attack, ischemic cerebrovascular accident, or hemorrhagic cerebrovascular accident. The association of HVAD with risk of NAE in the first year after implant was evaluated using propensity score matching to balance for preimplant risk factors. After matching, freedom from first major NAE in the HM3 and HVAD cohorts was compared with Kaplan-Meier curves. A secondary analysis using multivariable multiphase hazard models was used to identify predictors of NAE, which uses a data-driven parametric fit of the early declining and constant phase hazards and the associations of risk factor with either phase. RESULTS: Of 6205 included patients, 3129 (50.4%) received the HM3 and 3076 (49.6%) received the HVAD. Median follow-up was 9 and 12 months (HM3 and HVAD, respectively). Patients receiving HVAD had more major NAEs (16.4% versus 6.4%, P<0.001) as well as each subtype (transient ischemic attack: 3.3% versus 1.0%, P<0.001; ischemic cerebrovascular accident: 7.7% versus 3.4%, P<0.001; hemorrhagic cerebrovascular accident: 7.2% versus 2.0%, P<0.001) than did patients receiving HM3. A propensity-matched cohort balanced for preimplant risk factors showed that HVAD was associated with higher probabilities of major NAEs (% freedom from NAE 82% versus 92%, P<0.001). Device type was not significantly associated with NAEs in the early hazard phase, but HVAD was associated with higher incidence of major NAEs during the constant hazard phase (hazard ratio, 5.71 [CI, 3.90-8.36]). CONCLUSIONS: HM3 is associated with lower hazard of major NAEs than is HVAD beyond the early postimplantation period and during the constant hazard phase. Defining the explanation for this observation will inform device selection for individual patients.

Proceedings from the metrics forum in heart transplantation for performance monitoring.

Regulatory oversight for heart transplant programs is currently under review by the United Network for Organ Sharing (UNOS). There is concern whether 1-year patient and graft survival truly represent heart transplant center performance. Thus, a forum was organized by the Thoracic and Critical Care Community of Practice (TCC COP) of the American Society of Transplantation (AST) for the heart transplant community to voice their opinions on matters involving program performance monitoring by UNOS. A TCC COP work group was formed to review outcome metrics for adult heart transplantation and culminated in a virtual community forum (72 participants representing 61 heart transplant programs) on November 12-13, 2020. One-year posttransplant survival is still considered an appropriate and important measure to assess program performance. Waitlist mortality and offer acceptance rate as pretransplant metrics could also be useful measures of program performance, recognizing that outside factors may influence these metrics. In depth discussion of these metrics and other issues including auditing thresholds, innovations to reduce risk-averse behavior and personally designed program scorecards are included in this meeting proceedings.

Outcomes of infants with pulmonary atresia with intact ventricular septum listed for heart transplantation: A multi-institutional study.

BACKGROUND: Management of infants with pulmonary atresia/intact ventricular septum (PA/IVS) is variable. Because of higher mortality in more severe forms, heart transplant (HT) is an acceptable approach, but waitlist and post-transplant outcomes are unclear. This study compared outcomes of infants with PA/IVS vs. other single ventricle (SV) anatomies listed for HT. METHODS: Data from the Pediatric Heart Transplant Society (1993-2018) were analyzed for survival and risk factors for mortality. RESULTS: Of 1617 SV infants, 300 had PA/IVS (19%) and 1317 had other SV (81%). Overall, 1-, 5-, and 10-year survival was higher among PA/IVS (74%, 65%, 61%) versus other SV infants (62%, 54%, 50%, p = .004). While waitlist mortality was similar between groups (p = .09), PA/IVS was an independent predictor of improved waitlist survival (HR 0.68, p = .03), and PA/IVS infants had higher incidence of waitlist removal (8% vs. 5.5%, p = .03), most commonly for being "too well." Post-transplant survival was superior among PA/IVS versus other SV infants (1- and 5-year survival 93% and 81% vs. 80% and 71%, p < .0001). Risk factors for PA/IVS waitlist mortality (2008-2018) included extracorporeal membrane oxygenation and mechanical ventilation. Prior aortopulmonary (AP) shunt among PA/IVS infants was associated with improved waitlist survival. CONCLUSIONS: Overall survival among PA/IVS infants listed for HT exceeds that of other SV infants with PA/IVS identified as an independent predictor of improved waitlist and post-transplant survival. Prior AP shunt among listed PA/IVS infants was associated with improved waitlist outcomes, though, which may reflect a listing selection bias.

Obesity and dyslipidemia predict cardiac allograft vasculopathy and graft loss in children and adolescents post-heart transplant: A PHTS multi-institutional analysis.

BACKGROUND: Obesity and dyslipidemia afflict children of all ages. We explored the prevalence of obesity and dyslipidemia in pediatric heart transplant (HT) recipients and its effects on cardiac allograft vasculopathy (CAV) and survival. METHODS: This study included primary HT recipients (≤18 years) transplanted between 01/1996 and 12/2018 included in the Pediatric Heart Transplant Society database. Obesity was categorized according to WHO/CDC guidelines and dyslipidemia according to the National Cholesterol Education Program. Kaplan-Meier analyses for CAV and graft loss stratified for BMI and lipid panels were generated and risk factors identified using multivariate analyses. RESULTS: Among 6291 HT patients (median age [range] at HT = 4.3 [0.6-12.8] years; 45% Female; 68% White), 56% had a normal BMI at HT. Obese patients at HT had an increased risk for graft loss (HR 1.19, 95% CI 1.01-1.4, p = .04). Poor total cholesterol (TC), LDL-C, and TG were associated with the risk of both CAV (HR 1.79, p < .0001; HR 1.65, p = .0015; HR 1.53, p < .0001, respectively) and graft loss (HR 1.58, p = .0008; HR 1.22, p = .04; HR 1.43, p = .0007, respectively). CONCLUSIONS: Pediatric patients who are obese at the time of HT and dyslipidemic at 1 year post-HT are at an increased risk for CAV and graft loss. Preventative interventions may reduce morbidity and mortality among this cohort.

Excess heart age in young breast cancer survivors over 2-year follow-up.

BACKGROUND: Breast cancer survivors are at risk for developing cardiovascular disease due to cardiotoxic cancer treatment. Research on young breast cancer survivors (diagnosed < 45 years old) are limited. METHODS: Young breast cancer survivors diagnosed between age 30 and 44, stage I-III, and treated at the University of Alabama at Birmingham Hospital between 2012 and 2015 were included. Cardiovascular disease risk was estimated using excess heart age (calculated using age, systolic blood pressure, blood pressure medication, diabetes, smoking, body mass index) and examined at two time points: diagnosis and 2-year follow-up. Statistical analyses included within-group mean comparison tests and linear regression to examine predictors of excess heart age. RESULTS: A total of 152 young breast cancer survivors were included; 95 received anthracyclines and/or trastuzumab, and 57 did not. Overall excess heart age was 4.2 at diagnosis and 5.4 years at 2-year follow-up (p = 0.08). Change in excess heart age from diagnosis to 2-year follow-up among those receiving or not receiving anthracyclines and/or trastuzumab was 4.3-4.4 years, p = 0.93; and 4.0-7.1 years, p < 0.01; respectively. Factors that predicted excess heart age included endocrine therapy (p = 0.049) and change from premenopausal to postmenopausal status (p = 0.048). CONCLUSIONS: Anthracyclines and trastuzumab were not predictors of excess heart age. Subclinical changes undetected by heart age may still occur. Future research is needed to evaluate heart age over longer follow-up and to develop a modified heart age tool, that incorporates treatment risk, that facilitates identification of high-risk cancer patients for early intervention in cardiac risk prevention.

Race and Gender Disparities in Access to Parathyroidectomy: A Need to Change Processes for Diagnosis and Referral to Surgeons.

BACKGROUND: Hyperparathyroidism substantially impairs quality of life, and effective treatment depends on timely referral to surgeons. We hypothesized that there would be race and gender disparities in the time from initial diagnosis of hyperparathyroidism to treatment with parathyroidectomy. METHODS: We reviewed administrative data on 2289 patients with hypercalcemia (calcium > 10.5 mg/dL) and abnormal parathyroid hormone levels who were seen at a tertiary referral center from 2011 to 2016. We used two-phase parametric hazard modeling to identify predictors of time from index abnormal calcium until parathyroidectomy. RESULTS: The median age of our cohort was 63 years, and 1685 (74%) were women. Of the total patients, 1301 (57%) were Caucasian, and 946 (41%) were African-American. Only 490 (21%) patients underwent parathyroidectomy. Among patients undergoing surgery, time from index high calcium to surgical treatment was longest for African-American men, who waited a median of 13.6 months (interquartile range IQR 2-28), compared with 2.9 months (IQR 1-8) for Caucasian males (p < 0.05). African-American women waited a median of 6.7 months (IQR 2-16) versus 3.5 months (IQR 2-14) for Caucasian women (p < 0.05). At 1 year after the index abnormal calcium, only 6% of black men underwent surgery compared with 20% of white males (p < 0.05). Similarly, 13% of black women underwent surgery versus 20% of white women (p < 0.05). These differences remained significant after adjusting for age, calcium levels, insurance, and comorbidities. CONCLUSIONS: African-Americans face substantial delays in access to parathyroidectomy after diagnosis with hyperparathyroidism that could impair quality of life and increase health care costs. We must improve systems of diagnosis and referral to ensure timely treatment of hyperparathyroidism.

Fontan-associated plastic bronchitis waitlist and heart transplant outcomes: A PHTS analysis.

Plastic bronchitis is a rare post-Fontan complication with limited treatment options. Heart transplantation has evolved as a potential curative option, but outcomes have not been well-defined. This study aims to assess contemporary waitlist and post-transplant outcomes in patients with plastic bronchitis. All Fontan patients were identified in the PHTS database (2010 - 2018). Waitlist and post-transplant outcomes were compared between Fontan patients with and without plastic bronchitis. Competing outcomes and Kaplan-Meier analyses were used to assess the impact of plastic bronchitis on waitlist and post-transplant survival. A secondary analysis excluded those with PLE from the comparison cohort. Of 645 Fontan patients listed for heart transplant, 69 (11%) had plastic bronchitis. At listing, patients with plastic bronchitis were younger (8.9 vs 11.1 years, P = .02), but had few other differences in baseline characteristics. A fewer Fontan patients with plastic bronchitis were listed in the more recent era (46 [15.4%] in 2010-2014 vs 23 [6.6%] in 2015-2018, P < .01). Overall, there was no difference in waitlist (P = .30) or post-transplant (P = .66) survival for Fontan patients with and without plastic bronchitis. The results were similar after excluding patients with PLE. Contrary to prior reports, this relatively large series showed that plastic bronchitis did not have a negative impact on survival to or after heart transplantation in Fontan patients. Our study also found a 50% reduction in listing in the current era, which may indicate evolution in management of Fontan patients.

Examining racial and socioeconomic disparity in the pediatric heart transplant evaluation.

Racial disparities have been reported among pediatric patients waitlisted for and undergoing heart transplantation but have not been studied further upstream in the transplant candidate evaluation process. We retrospectively studied our single-center experience in order to investigate any potential biases in the evaluation process. Results of the heart transplant evaluation in children ≤18 years old at our institution were analyzed. Primary outcome was final disposition to waitlist or not. Race was defined by family self-identification. Descriptive and comparative statistical analyses were performed. From 2013 to 2019, 133 unique patients were referred for listing consideration. While Black patients comprised 44% of the referral population and had more markers of socioeconomic disadvantage, they comprised 43% of the patients who were listed for transplantation with no significant difference between these proportions (p = .96). Black and White patients made up a similar proportion of patients deemed too well or too ill for listing. Black patients had lower annual household income estimates and rates of household marriage. Despite identifying significant social challenges in 27 patients (18 of them Black), only five patients (3 Black and 2 White) were turned down for listing due to social barriers. While limited by the small number of patients turned down for social barriers, our transplant evaluation process does not appear to result in racial disparities in access to listing. Further studies are needed using national cohorts to explore possible racial disparities upstream from waitlisting and transplantation, such as during the referral and evaluation.