Reduced incidence of cardiac rejection in multi-organ transplants: A propensity matched study.

2023

e15019

05/2023

1399-0012

BACKGROUND: Rejection remains a primary cause of graft loss after heart transplant (HT). Recognizing the immunomodulation of multi-organ transplant can enhance our understanding of the mechanisms of cardiac rejection.

METHODS: This retrospective cohort study identified patients from the UNOS database with isolated heart (H, N = 37 433), heart-kidney (HKi, N = 1516), heart-liver (HLi, N = 286), and heart-lung (HLu, N = 408) transplants from 2004 to 2019. Propensity score matching reduced baseline differences between groups. Outcomes included risk of rejection prior to transplant hospital discharge and within 1 year, and mortality within 1 year of transplant.

RESULTS: In the propensity score matched data, the relative risk of being treated for rejection prior to transplant hospital discharge was 61% lower for HKi (RR .39, 95% CI .29, .53) and 87% lower for HLi (RR .13, 95% CI .05, .37) compared to H. Similarly, the probability of being treated for rejection in the first year after transplant remained lower in HKi (RR .45, 95% CI .35, .57) and HLi (RR .13, 95% CI .06, .28) compared to H. The 1-year survival analysis revealed an equivalent risk of death in HKi (HR .84, 95% CI .68, 1.03) and HLi (HR 1.41, 95% CI .83, 2.41) compared to H, while HLu had a higher risk of death in the first year after transplant (HR 1.65, 95% CI 1.17, 2.33).

CONCLUSIONS: Recipients of HKi and HLi experience a reduced risk of rejection when compared to H, but an equivalent risk of 1 yr mortality. These findings have important implications for the future of HT medicine.

10.1111/ctr.15019

Clin Transplant

37212365

Temporal trends in primary payers in pediatric heart transplant and association with long-term survival.

2023

e14484

05/2023

1399-3046

BACKGROUND: Pediatric heart transplantation (HT) is resource intensive. In adults, there has been an increase in the proportion of HTs funded by public insurance, with post-HT outcomes inferior to those funded by private sources. Trends in the funding of pediatric HT and outcomes in children have not been described.

METHODS: We queried the United Network for Organ Sharing (UNOS) database for children (<18 years) listed for and undergoing HT between 2004 and 2021. We identified the primary payer at listing, HT, 1 year, and 1-5 years following HT. Trends were analyzed using generalized logit models. Multivariable-extended Cox regression models were used to test the relationship between insurance type at the time of transplant and time to death or re-transplant.

RESULTS: There were 6382 pediatric patients who underwent transplants and had either public or private insurance at the time of transplant. The percentage of patients with public insurance at the time of HT increased over time. Public insurance at the time of HT was associated with an increased risk of death or re-transplant beyond 2 months after HT (adjusted HR at 6 months = 1.43, 95% CI: 1.13-1.81, p = .003; adjusted HR at 9 months = 1.67, 95% CI: 1.17-2.37, p = .004).

CONCLUSION: There has been a statistically significant trend toward increasing public insurance for children awaiting, at the time of, and after HT. Black patients and those with public insurance at HT have worse long-term outcomes. This study highlights ongoing disparities in pediatric HT and the need to focus efforts on achieving equitable outcomes.

10.1111/petr.14484

Pediatr Transplant

36751006

Factors associated with discontinuation of pulmonary vasodilator therapy in children with bronchopulmonary dysplasia-associated pulmonary hypertension.

2022

1246-1254

06/2022

1476-5543

OBJECTIVE: To evaluate factors associated with discontinuation of pulmonary vasodilator therapy in bronchopulmonary dysplasia-related pulmonary hypertension (BPD-PH).

STUDY DESIGN: Retrospective study of neonatal, echocardiographic, and cardiac catheterization data in 121 infants with BPD-PH discharged on pulmonary vasodilator therapy from 2009-2020 and followed into childhood.

RESULT: After median 4.4 years, medications were discontinued in 58%. Those in whom medications were discontinued had fewer days of invasive support, less severe BPD, lower incidence of PDA closure or cardiac catheterization, and higher incidence of fundoplication or tracheostomy decannulation (p < 0.05). On multivariable analysis, likelihood of medication discontinuation was lower with longer period of invasive respiratory support [HR 0.95 (CI:0.91-0.99), p = 0.01] and worse RV dilation on pre-discharge echocardiogram [HR 0.13 (CI:0.03-0.70), p = 0.017]. In those with tracheostomy, likelihood of medication discontinuation was higher with decannulation [HR 10.78 (CI:1.98-58.59), p < 0.001].

CONCLUSION: In BPD-PH, childhood discontinuation of pulmonary vasodilator therapy is associated with markers of disease severity.

10.1038/s41372-022-01421-6

J Perinatol

35676536

Center Variation in Indication and Short-Term Outcomes after Pediatric Heart Transplantation: Analysis of a Merged United Network for Organ Sharing - Pediatric Health Information System Cohort.

2021

2021 Nov 15

1432-1971

<p>The relationship between center-specific variation in indication for pediatric heart transplantation and short-term outcomes after heart transplantation is not well described. We used merged patient- and hospital-level data from the United Network for Organ Sharing and the Pediatric Health Information Systems to analyze outcomes according to transplant indication for a cohort of children (≤ 21&nbsp;years old) who underwent heart transplantation between 2004 and 2015. Outcomes included 30-day mortality, transplant hospital admission mortality, and hospital length of stay, with multivariable adjustment performed according to patient and center characteristics. The merged cohort reflected 2169 heart transplants at 20 U.S. centers. The median number of transplants annually at each center was 11.6, but ranged from 3.5 to 22.6 transplants/year. Congenital heart disease was the indication in the plurality of cases (49.2%), with cardiomyopathy (46%) and myocarditis (4.8%) accounting for the remainder. There was significant center-to-center variability in congenital heart disease as the principal indication, ranging from 15% to 66% (P &lt; 0.0001). After adjustment, neither center volume nor proportion of indications for transplantation were associated with 30-day or transplant hospital admission mortality. In this large, merged pediatric cohort, variation was observed at center level in annual transplant volume and prevalence of indications for heart transplantation. Despite this variability, center volume and proportion of indications represented at a given center did not appear to impact short-term outcomes.</p>

10.1007/s00246-021-02768-x

Pediatr Cardiol

34779880

Depression and Anxiety Symptoms During and After Pediatric Asthma Hospitalization.

2021

2021 Oct 20

2154-1671

<p><strong>OBJECTIVES: </strong>Depression and anxiety are common in children with asthma, and asthma hospitalization is an underused opportunity to identify mental health concerns. We assessed depression and anxiety symptoms during asthma hospitalization and 1 to 2 months post discharge.</p>

<p><strong>METHODS: </strong>This prospective cohort study included children aged 7 to 17 years who were hospitalized for asthma exacerbation. Participants completed the self-report PROMIS (Patient-Reported Outcomes Measurement Information System) depression and anxiety symptom scales (T score mean = 50, SD = 10) during hospitalization and 1 to 2 months after discharge. Higher scores indicate more symptoms and/or greater severity. We compared patients' scores during hospitalization and at follow-up using paired tests and examined individual patients' depression and anxiety symptom trajectories using a Sankey diagram.</p>

<p><strong>RESULTS: </strong>Among 96 participants who completed the study, 53% had elevated symptoms of depression, anxiety, or both either during hospitalization or after discharge. During hospitalization, 38% had elevated depression symptoms and 45% had elevated anxiety symptoms. At postdischarge follow-up, 18% had elevated depression symptoms and 20% had elevated anxiety symptoms. We observed all possible symptom trajectories: symptoms during hospitalization that persisted (especially if both depression and anxiety symptoms were present), symptoms that resolved, and symptoms that were present at follow-up only.</p>

<p><strong>CONCLUSIONS: </strong>Just more than half of youth hospitalized for asthma exacerbation experienced depression and/or anxiety symptoms during hospitalization or at follow-up. Patients who had both depression and anxiety symptoms during hospitalization were the most likely to have persistent symptoms at follow-up. Screening at both time points may be useful to identify mental health symptoms.</p>

10.1542/hpeds.2020-000950

Hosp Pediatr

34670757

Identifying Risk Factors for Complicated Post-operative Course in Tetralogy of Fallot Using a Machine Learning Approach.

2021

685855

2021

2297-055X

<p>Tetralogy of Fallot (TOF) repair is associated with excellent operative survival. However, a subset of patients experiences post-operative complications, which can significantly alter the early and late post-operative course. We utilized a machine learning approach to identify risk factors for post-operative complications after TOF repair. We conducted a single-center prospective cohort study of children &lt;2 years of age with TOF undergoing surgical repair. The outcome was occurrence of post-operative cardiac complications, measured between TOF repair and hospital discharge or death. Predictors included patient, operative, and echocardiographic variables, including pre-operative right ventricular strain and fractional area change as measures of right ventricular function. Gradient-boosted quantile regression models (GBM) determined predictors of post-operative complications. Cross-validated GBMs were implemented with and without a filtering stage non-parametric regression model to select a subset of clinically meaningful predictors. Sensitivity analysis with gradient-boosted Poisson regression models was used to examine if the same predictors were identified in the subset of patients with at least one complication. Of the 162 subjects enrolled between March 2012 and May 2018, 43 (26.5%) had at least one post-operative cardiac complication. The most frequent complications were arrhythmia requiring treatment ( = 22, 13.6%), cardiac catheterization ( = 17, 10.5%), and extracorporeal membrane oxygenation (ECMO) ( = 11, 6.8%). Fifty-six variables were used in the machine learning analysis, of which there were 21 predictors that were already identified from the first-stage regression. Duration of cardiopulmonary bypass (CPB) was the highest ranked predictor in all models. Other predictors included gestational age, pre-operative right ventricular (RV) global longitudinal strain, pulmonary valve Z-score, and immediate post-operative arterial oxygen level. Sensitivity analysis identified similar predictors, confirming the robustness of these findings across models. Cardiac complications after TOF repair are prevalent in a quarter of patients. A prolonged surgery remains an important predictor of post-operative complications; however, other perioperative factors are likewise important, including pre-operative right ventricular remodeling. This study identifies potential opportunities to optimize the surgical repair for TOF to diminish post-operative complications and secure improved clinical outcomes. Efforts toward optimizing pre-operative ventricular remodeling might mitigate post-operative complications and help reduce future morbidity.</p>

10.3389/fcvm.2021.685855

Front Cardiovasc Med

34368247

Resource utilization in children with paracorporeal continuous-flow ventricular assist devices.

2021

2021 Feb 22

1557-3117

<p><strong>BACKGROUND: </strong>Paracorporeal continuous-flow ventricular assist devices (PCF VAD) are increasingly used in pediatrics, yet PCF VAD resource utilization has not been reported to date.</p>

<p><strong>METHODS: </strong>Pediatric Interagency Registry for Mechanically Assisted Circulatory Support (PediMACS), a national registry of VADs in children, and Pediatric Health Information System (PHIS), an administrative database of children's hospitals, were merged to assess VAD implants from 19 centers between 2012 and 2016. Resource utilization, including hospital and intensive care unit length of stay (LOS), and costs are analyzed for PCF VAD, durable VAD (DVAD), and combined PCF-DVAD support.</p>

<p><strong>RESULTS: </strong>Of 177 children (20% PCF VAD, 14% PCF-DVAD, 66% DVAD), those with PCF VAD or PCF-DVAD are younger (median age 4 [IQR 0-10] years and 3 [IQR 0-9] years, respectively) and more often have congenital heart disease (44%; 28%, respectively) compared to DVAD (11 [IQR 3-17] years; 14% CHD); p &lt; 0.01 for both. Median post-VAD LOS is prolonged ranging from 43 (IQR 15-82) days in PCF VAD to 72 (IQR 55-107) days in PCF-DVAD, with significant hospitalization costs (PCF VAD $450,000 [IQR $210,000-$780,000]; PCF-DVAD $770,000 [IQR $510,000-$1,000,000]). After adjusting for patient-level factors, greater post-VAD hospital costs are associated with LOS, ECMO pre-VAD, greater chronic complex conditions, and major adverse events (p &lt; 0.05 for all). VAD strategy and underlying cardiac disease are not associated with LOS or overall costs, although PCF VAD is associated with higher daily-level costs driven by increased pharmacy, laboratory, imaging, and clinical services costs.</p>

<p><strong>CONCLUSION: </strong>Pediatric PCF VAD resource utilization is staggeringly high with costs primarily driven by pre-implantation patient illness, hospital LOS, and clinical care costs.</p>

10.1016/j.healun.2021.02.011

J Heart Lung Transplant

33744087

The Impact of Syndromic Genetic Disorders on Medical Management and Mortality in Pediatric Hypertrophic Cardiomyopathy Patients.

2020

2020 May 30

1432-1971

<p>Hypertrophic cardiomyopathy (HCM) is a prevalent cardiomyopathy in children, with variable etiologies, phenotypes, and associated syndromic genetic disorders (GD). The spectrum of evaluation in this heterogeneous population has not been well described. We aimed to describe mortality and medical management in the pediatric HCM population, and compare HCM pediatric patients with GD to those without GD. Children (&lt; 18&nbsp;years) with HCM from the claims-based Truven Health Analytics MarketScan Research Database for years 2013-2016 were identified. Outcomes, including patient visits, diagnostic tests, procedures, medications, and mortality, were reported across demographic and clinical characteristics. Multivariable negative binomial, logistic, and survival models were utilized to test the association between those with and without GD by outcomes. 4460 patients were included, with a median age of 11&nbsp;years (IQR 3-16), 61.7% male, 17.7% with GD, and 2.1% who died during the study period. There were 0.36 inpatient admissions per patient-year. Patients with GD were younger [8&nbsp;years (IQR 1-14) vs 12&nbsp;years (IQR 3-16) (p &lt; 0.0001)], had more echocardiograms (1.77 vs 0.93) p &lt; 0.0001; and ambulatory cardiac monitoring per year (0.32 vs 0.24); p = 0.0002. Adjusting for potential confounders including age, other chronic medical conditions, procedures, and heart failure, GD had increased risk of mortality [HR 2.46 (95% CI 1.62, 3.74)], myectomy [HR 1.59 (95% CI 1.08, 2.35)], and more annual admissions [OR 1.36 (CI 1.27, 1.45]. Patients with HCM show higher rates of death, admission, testing, and myectomy when concomitant syndromic genetic disorders are present, suggesting that the disease profile and resource utilization are different from HCM patients without GD.</p>

10.1007/s00246-020-02373-4

Pediatr Cardiol

32474737

A Comparison of Bidirectional Glenn vs. Hemi-Fontan Procedure: An Analysis of the Single Ventricle Reconstruction Trial Public Use Dataset.

2020

2020 May 29

1432-1971

<p>Patients with single ventricle (SV) heart defects have two primary surgical options for superior cavopulmonary connection (SCPC): bidirectional Glenn (BDG) and hemi-Fontan (HF). Outcomes based on type of SCPC have not been assessed in a multi-center cohort. This retrospective cohort study uses the Single Ventricle Reconstruction (SVR) Trial public use dataset. Infants who survived to SCPC were evaluated through 1&nbsp;year of age, based on type of SCPC. The primary outcome was transplant-free survival at 1&nbsp;year. The cohort included 343 patients undergoing SCPC across 15 centers in North America; 250 (73%) underwent the BDG. There was no difference between the groups in pre-SCPC clinical characteristics. Cardiopulmonary bypass times were longer [99&nbsp;min (IQR 76, 126) vs 81&nbsp;min (IQR 59, 116), p &lt; 0.001] and use of deep hypothermic circulatory arrest (DHCA) more prevalent (51% vs 19%, p &lt; 0.001) with HF. Patients who underwent HF had a higher likelihood of experiencing more than one post-operative complication (54% vs 41%, p = 0.05). There were no other differences including the rate of post-operative interventional cardiac catheterizations, length of stay, or survival at discharge, and there was no difference in transplant-free survival out to 1&nbsp;year of age. Mortality after SCPC is low and there is no difference in mortality at 1&nbsp;year of age based on type of SCPC. Differences in support time and post-operative complications support the preferential use of the BDG, but additional longitudinal follow-up is necessary to understand whether these differences have implications for long-term outcomes.</p>

10.1007/s00246-020-02371-6

Pediatr Cardiol

32472151

Pediatric In-Hospital CPR Quality at Night and on Weekends.

2019

2019 Nov 14

1873-1570

<p><strong>INTRODUCTION: </strong>Survival after in-hospital cardiac arrest (IHCA) has been reported to be worse for arrests at night or during weekends.This study aimed to determine whether measured cardiopulmonary resuscitation (CPR) quality metrics might explain this difference in outcomes.</p>

<p><strong>METHODS: </strong>IHCA data was collected by the Pediatric Resuscitation Quality (pediRES-Q) collaborative for patients &lt;18 years. Metrics of CPR quality [chest compression rate, depth and fraction] were measured using monitordefibrillator pads, and events were compared by time of day and day of week.</p>

<p><strong>RESULTS: </strong>We evaluated 6915 sixty-second epochs of chest compression (CC) data from 239 subjects between October 2015 and March 2019, across 18 hospitals. There was no significant difference in CPR quality metrics during day (07:00-22:59) versus night (23:00-06:59), or weekdays (Monday 07:00 to Friday 22:59) versus weekends (Friday 23:00 to Monday 06:59).There was also no difference in rate of return of circulation. However, survival to hospital discharge was higher for arrests that occurred during the day (39.1%) vs. nights (22.4%, p = 0.015), as well as on weekdays (39.9%) vs. weekends (19.1%, p = 0.003).</p>

<p><strong>CONCLUSIONS: </strong>For pediatric IHCA where CC metrics were obtained, there was no significant difference in CPR quality metrics or rate of return of circulation by time of day or day of week. There was higher survival to hospital discharge when arrests occurred during the day (vs. nights), or on weekdays (vs. weekends), and this difference was not related to disparities in CC quality.</p>

10.1016/j.resuscitation.2019.10.039

Resuscitation

31734222