Risk Factors For Waitlist Mortality Research Articles

NAFLD: A pretransplant and post-transplant conundrum.

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Model for End-Stage Liver Disease/Pediatric End-Stage Liver Disease exception policy and outcomes in pediatric patients with hepatopulmonary syndrome requiring liver transplantation.

Hepatopulmonary syndrome (HPS) is associated with increased waitlist mortality in liver transplantation (LT) candidates. Children with HPS are granted Model for End-Stage Liver Disease (MELD)/Pediatric End-Stage Liver Disease (PELD) exception points for waitlist prioritization in the United States based on criterion developed for adults. In this study, the impact of this MELD/PELD exception policy on post-LT survival in children was examined. A retrospective cohort of patients aged younger than 18 years with a MELD/PELD exception request who underwent LT between 2007 and 2018 were identified in the Scientific Registry of Transplant Recipients. Patients were stratified by waitlist partial pressure of arterial oxygen (PaO 2 ) to assess risk factors for waitlist mortality and post-LT survival. Among 3082 pediatric LT recipients included in the study, 124 patients (4%) received MELD/PELD exception points for HPS. Patients with HPS were a median age of 9 years (interquartile range: 6, 12 years), 54.8% were girls, and 54% were White. Most patients (87.9%) were listed with laboratory MELD/PELD scores <15. Waitlist mortality for patients with HPS exception points was rare and not different from patients without HPS. When stratified by pre-LT PaO 2 , hypoxemia severity was not associated with differences in 1-, 3-, or 5-year survival rates after LT ( p = 0.13). However, patients with HPS showed a slightly lower survival rate at 5 years compared with patients without HPS (88.7% vs. 93.4%; p = 0.04). MELD/PELD exceptions for children with HPS mitigated waitlist mortality, and recipients with HPS experienced excellent 5-year survival after LT, although slightly lower than in patients without HPS. Unlike adults with HPS, the severity of pre-LT hypoxemia in children does not impact post-LT survival. These data suggest that adult criteria for granting MELD/PELD exception points may not appropriately capture HPS severity in pediatric patients. Further prospective multicenter studies to examine the risk factors predicting negative survival outcomes in children with HPS are warranted.

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.

Outcomes of patients awaiting lung transplantation after the implementation of donation after brain death at a single Chinese center.

Voluntary contribution has become the only source of donor lungs in China since 2015. To elaborate the outcomes of patients awaiting lung transplantation (LTx) after the implementation of donation after brain death, we performed a retrospective study that encompassed 205 patients with end-stage lung disease who registered for LTx at Shanghai Pulmonary Hospital from January 1, 2015 to January 1, 2021. A total of 180 patients were enrolled in the study. The median waiting time was 1.25 months. Interstitial lung disease (ILD) (103/180, 57.2%) and chronic obstructive pulmonary disease (COPD) (56/180, 31.1%) were the most common diseases in our study population. The mean pulmonary artery pressure (mPAP) of patients in the died-waiting group was higher than that of the survivors (53.29±21.71 mmHg vs. 42.11±18.58 mmHg, P=0.002). The mortality of patients with ILD (34/103, 33.00%) was nearly twice that of patients with COPD (10/56, 17.86%) while awaiting LTx (P=0.041). In the died-waiting group, patients with ILD had a shorter median waiting time than patients with COPD after being listed (0.865 months vs. 4.720 months, P=0.030). ILD as primary disease and mPAP > 35 mmHg were two significant independent risk factors for waitlist mortality, with hazard ratios (HR) of 3.483 (95% CI 1.311-9.111; P=0.011) and 3.500 (95% CI 1.435-8.536; P=0.006). Hence, LTx is more urgently needed in patients with ILD and pulmonary hypertension.

A Simple Scoring System for Lung Transplant Waitlist Mortality Risk Factors

<h3>Purpose</h3> Current lung allocation score (LAS) waitlist mortality prediction models are complex and incorporate correlated predictors. This study identified and evaluated three multidimensional indices of correlated risk factors. This approach could enable more efficient use of risk factor information and improve dynamic models of end-stage lung disease and transplant outcomes. <h3>Methods</h3> We analyzed 2015-2020 data on U.S. lung transplant candidates on the waiting list, obtained from the Scientific Registry for Transplant Recipients (N=13990). We used hierarchical clustering to identify distinct respiratory support groups based on supplemental oxygen device, rate and frequency of use; steroid use and extracorporeal membrane oxygenation. We used confirmatory factor analysis (CFA) to derive indices of i) airway function (forced expiratory volume, forced vital capacity, and partial pressure of carbon dioxide [PCO₂]) and ii) oxygen function (partial pressures of oxygen (PO₂), PO₂/FiO₂ ratio, and mean pulmonary artery pressure). Cox proportional hazards regression was used to characterize relationships between the developed constructs and waitlist mortality (or removal) after adjusting for disease group, age and sex. <h3>Results</h3> Four respiratory support clusters were identified (see the panel labels in the <b>Figure</b>). Contours of predicted 6-month waitlist mortality risk are displayed for a sample 63-year-old patient with idiopathic pulmonary fibrosis in the Figure. The area under the receiver-operating characteristic curve [95% confidence interval] for 1-year predictions from the fitted Cox model was 0.75 [0.71, 0.79], which was marginally lower than that of the full LAS waitlist mortality model (AUC = 0.79 [0.75, 0.83]). <h3>Conclusion</h3> The three developed constructs of respiratory support, oxygen function and airway function distilled information in 11 correlated risk factors for waitlist mortality, facilitating interpretation of risk profiles without adversely impacting model accuracy. <h3>Funding</h3> NIH R01HL15375

Trends and outcomes following total artificial heart as bridge to transplant from the UNOS database.

Bridge to transplantation (BTT) with a SynCardia Total Artificial Heart (TAH) has been gaining momentum as a therapy for patients with biventricular heart failure. Recent transplant waitlist and posttransplant outcomes with this strategy have not been comprehensively characterized. We reviewed the United Network for Organ Sharing (UNOS) database to examine BTT outcomes for the TAH system since approval. Adult patients listed for heart transplantation in the UNOS system between 2004 and 2020 who underwent BTT therapy with a TAH were included in the study. Trends in utilization of TAH compared with other durable mechanical support strategies were examined. The primary outcome was 1-year survival following heart transplantation following BTT with TAH. Secondary outcomes included waitlist deterioration and risk factors for waitlist or posttransplant mortality. During the study 433 total patients underwent TAH implant as BTT therapy; 236 (54.4%) were listed with the TAH, while the remaining patients were upgraded to TAH support while on the waitlist. Waitlist mortality was 7.4%, with 375 patients (86.6%) ultimately being transplanted. Age, cerebrovascular disease, functional status, and ventilator dependence were risk factors for waitlist mortality. One-year survival following successful BTT was 80%. Risk factors for mortality following BTT included age, body mass index, and underlying diagnosis. Patients undergoing BTT with TAH demonstrate acceptable waitlist survival and good 1-year survival. While utilization initially increased as a BTT therapy, there has been a plateau in relative utilization. Individual patient and transplantation center factors deserve further investigation to determine the ideal population for this therapy.

Waiting time and mortality rate on lung transplant candidates in Japan: a single-center retrospective cohort study

BackgroundAs lung transplantation (LTX) is a valuable treatment procedure for end-stage pulmonary disease, delayed referral to a transplant center should be avoided. We aimed to conduct a single-center analysis of the survival time after listing for LTX and waitlist mortality in each disease category in a Japanese population.MethodsWe included patients listed for LTX at Tohoku University Hospital from January 2007 to December 2020 who were followed up until March 2021. Pulmonary disease was categorized into the Obstructive, Vascular, Suppurative, Fibrosis, and Allogeneic groups. Risk factors for waitlist mortality were assessed using a Cox proportional hazards model. The Kaplan–Meier method was used to model time to death.ResultsWe included 269 LTX candidates. Of those, 100, 72, and 97 patients were transplanted, waiting, and dead, respectively. The median time to LTX and time to death were 796 days (interquartile range [IQR] 579–1056) and 323 days (IQR 129–528), respectively. The Fibrosis group showed the highest mortality (50.9%; p < .001), followed by the Allogeneic (35.0%), Suppurative (33.3%), Vascular (32.1%), and Obstructive (13.1%) groups. The Fibrosis group showed a remarkable risk for waitlist mortality (hazard ratio 3.32, 95% CI 2.11–4.85).ConclusionsIn Japan, the waiting time is extremely long and candidates with Fibrosis have high mortality. There is a need to document outcomes based on the underlying disease for listed LTX candidates to help determine the optimal timing for listing patients based on the estimated local waiting time.

Mortality Determinants in Children with Biliary Atresia Awaiting Liver Transplantation

To determine risk factors for waitlist mortality in children with biliary atresia listed for liver transplantation. There were 2704 children with biliary atresia (<12years of age) listed for a first liver transplant (2002-2018) in the United Network for Organ Sharing database. Fine-Gray regression models for competing risks analysis (main risk=waitlist mortality/delisting owing to too sick; competing risk=liver transplantation) were implemented to identify risk factors for waitlist mortality. The median waitlist time was 83days (IQR, 34-191). The cumulative incidence of waitlist mortality was 5.2%. In multivariable analysis (n=2253), increasing bilirubin level (P<.001), portal vein thrombosis (P=.03), and ventilator dependence (P<.001) at listing were associated with a higher risk, whereas weight ≥10kg at listing (P=.009) was associated with a lower risk of waitlist mortality. When ascites at listing was included in multivariable analysis (n=1376), it was associated with a higher risk for the composite outcome (P=.03). Encephalopathy at listing was not associated with waitlist mortality (n=1376; P=.15). These parameters can be used to more objectively prioritize children with biliary atresia awaiting liver transplantation and identify children with biliary atresia-related end-stage liver disease at high-risk of mortality.

Variables Associated With Cardiac Surgical Waitlist Mortality From a Population-Based Cohort

BackgroundCardiac surgery waitlist recommendations, which were developed based on expert opinion, poorly predict preoperative mortality. Studies reporting risk factors for waitlist mortality have not evaluated the risks including nonadherence to waitlist benchmarks. MethodsIn patients who underwent cardiac surgery or died on the waitlist between 2005 and 2015, we used a Fine and Gray competing risk model to identify independent predictors of waitlist mortality in 12,106 patients scheduled for urgent, semiurgent, or nonurgent surgery. The predictive variables were compared with Canadian Cardiovascular Society (CCS) waitlist recommendations using the Akaike information criterion. ResultsA total of 101 (0.8%) patients died awaiting surgery. The median wait times and frequency waitlist deaths among emergent, urgent, semi-urgent, and nonurgent surgery were 0.6, 7.4, 69.0, 55.5 days (P < 0.001) and 6.3%, 0.8%, 0.3%, 0.6% (P < 0.001), respectively. Adherence to CCS waitlist recommendations was higher in patients who died on the waitlist (51.6% vs 70.8%, P = 0.001) and was not predictive of waitlist mortality (hazard ratio 1.48, 95% confidence interval 0.62-0.56). Independent predictors of waitlist mortality were age, aortic surgery, ejection fraction < 35%, urgent surgery, prior myocardial infarction, haemodynamic instability during cardiac catheterization, hypertension, and dyslipidemia. These variables were superior to current CCS guidelines (Akaike information criterion 1251 vs 1317, likelihood ratio test P < 0.001). ConclusionsCCS waitlist recommendations were poorly predictive of waitlist mortality and the majority of waitlist deaths occur within recommended benchmarks. We identified variables associated with waitlist mortality with improved clinical performance. Our findings suggest a need to re-evaluate cardiac surgical triage criteria using evidence-based data.

Effects of Allocating Livers for Transplantation Based on Model for End-Stage Liver Disease–Sodium Scores on Patient Outcomes

The Model for End-stage Liver Disease and Sodium (MELD-Na) score was introduced for liver allocation in January 2016. We evaluated the effects of liver allocation, based on MELD-Na score, on waitlist and post-transplantation outcomes. We examined 2 patient groups from the United Network for Organ Sharing registry; the MELD-period group was composed of patients who were registered as transplant candidates from June 18, 2013 through January 10, 2016 (n= 18,850) and the MELD-Na period group was composed of patients who were registered from January 11, 2016 through September 30, 2017 (n= 14,512). We compared waitlist and post-transplantation outcomes and association with serum sodium concentrations between groups. Mortality within 90 days on the liver waitlist decreased (hazard ratio [HR] 0.738, P < .001) and transplantation probability increased significantly (HR 1.217, P < .001) in the MELD-Na period. Although mild, moderate, and severe hyponatremia (130-134, 125-129, and <125 mmol/L) were independent risk factors for waitlist mortality in the MELD period (HR 1.354, 1.762, and 2.656; P< .001, P < .001, and P < .001, respectively) compared with the reference standard (135-145 mmol/L), these adverse outcomes were decreased in the MELD-Na period (HR 1.092, 1.271 and 1.374; P= .27, P= .018, and P= .037, respectively). The adjusted survival benefit of transplant recipients vs patients placed on the waitlist in thesame scorecategories was definitive for patients with MELD-Na scores of 21-23 in the MELD-Na era (HR 0.336, P<.001) compared with MELD scores of 15-17 in the MELD era (HR0.365, P < .001). Liver allocation basedon MELD-Na score successfully improved waitlist outcomes and provided significant benefit to hyponatremic patients. Given the discrepancy in transplantation survival benefit, the current rules for liver allocation might require revision.

Waiting list outcomes in pediatric lung transplantation: Poor results for children listed in adult transplant programs

Low case volume has been associated with lower survival after pediatric lung transplantation. Our aim was to analyze waitlist outcomes among pediatric lung transplant centers in the USA. We studied a cohort of 1,139 pediatric candidates listed in the Organ Procurement and Transplantation Network for lung transplantation between 2002 and 2014. Of these candidates, 720 (63.2%) received a transplant. Candidates were divided into groups according to the clinical activity of the center of listing: high-volume pediatric (≥4 transplants per year); low-volume pediatric (<4 transplants per year); and adult (transplant volume predominantly in adults). We used multivariate Cox regression analysis to identify independent risk factors for waitlist mortality. We also determined the transplant rate-or likelihood of transplant after listing-over the study period. Fifty-eight percent of the children and adolescents were listed in adult centers where the resultant transplant rate was low-only 42% received a transplant compared with 93% in pediatric programs. Listing in an adult program was also the most significant risk factor for death on the waiting list (hazard ratio 15.6, 95% confidence interval 5.8 to 42.1). Most children (58%) are listed for lung transplantation in adult centers and have a reduced rate of transplantation and a greater chance of waitlist mortality.

Differential effect of body mass index on pediatric heart transplant outcomes based on diagnosis.

The impact of nutritional status on HTx waitlist mortality in children is unknown, and there are conflicting data regarding the role of nutrition in post-HTx survival. This study examined the influence of nutrition on waitlist and post-HTx outcomes in children. Children 2-18yr listed for HTx from 1997 to 2011 were identified from the OPTN database and stratified by BMI percentile. Multivariable logistic regression evaluated the influence of BMI on waitlist mortality. Cox proportional hazard regression assessed the impact of BMI on post-HTx mortality. When all 2712 patients were analyzed, BMI did not impact waitlist, one-, or five-yr mortality. However, when stratified by diagnosis, BMI>95% (AOR 1.96; 95% CI 1.24, 3.09) and BMI<1% (AOR 2.17; 95% CI 1.28, 3.68) were independent risk factors for waitlist mortality in patients with CM. BMI did not impact waitlist mortality in CHD and did not impact post-HTx outcomes, regardless of diagnosis. BMI>95% and BMI<1% are independent risk factors for waitlist mortality in patients with CM, but not CHD. This suggests differing risk factors based on disease etiology, and an individualized approach to risk assessment based on diagnosis may be warranted.

Abnormal nutrition affects waitlist mortality in infants awaiting heart transplant

Although nutritional status affects survival after heart transplant (HTx) in adults and older children, its effect on outcomes in young children is unknown. This study aimed to assess the effect of pre-HTx nutrition on outcomes in this population. Children aged 0 to 2 years old listed for HTx from 1997 to 2011 were identified from the Organ Procurement and Transplantation Network database. Nutritional status was classified according to percentage of ideal body weight at listing and at HTx. Logistic regression analysis evaluated the risk of waitlist mortality. Cox proportional hazard models assessed the effect of nutrition on post-HTx survival. Of 1,653 children evaluated, 899 (54%) had normal nutrition at listing, 445 (27%) were mildly wasted, 203 (12%) were moderate or severely wasted, and 106 (6%) had an elevated weight-to-height (W:H) ratio. Moderate or severe wasting (adjusted odds ratio, 1.9; 95% confidence interval, 1.3-2.7) and elevated W:H (adjusted odds ratio, 1.7; 95% confidence interval, 1.1-2.6) were independent risk factors for waitlist mortality. HTx was performed in 1,167 patients, and 1,016 (87%) survived to 1-year post-HTx. Nutritional status at listing or at HTx was not associated with increased post-HTx mortality. Nutritional status did not affect the need for early reoperation, dialysis, or the incidences of infection, stroke, or rejection before hospital discharge. Moderate or severe wasting and an elevated W:H are independent risk factors for waitlist mortality in patients aged < 2 years but do not affect post-HTx mortality. Optimization of pre-HTx nutritional status constitutes a strategy to reduce waitlist mortality in this age range.

The Effect of Nutritional Status on Heart Transplant Survival in Patients under Two Years of Age

Purpose Nutritional status has been shown to affect survival after heart transplant (HTx) in adults and older children. The impact of nutritional status on survival to HTx and HTx outcomes in children Methods and Materials Children 0-2 years listed for HTx from 1997-2011 were identified from the Organ Procurement and Transplantation Network database. Weight-for-height z-scores and percent ideal body weight (%IBW) were calculated at listing and at transplant. Nutritional status was categorized using the Waterlow criteria based on %IBW. The impact of nutritional status on survival to HTx was evaluated using logistic regression analysis and 1-year post-HTx survival was analyzed using Cox proportional hazard models. Results 1,653 children were included. At listing, 899 (55%) were categorized as normal nutrition status, 445 (27%) mildly wasted, 203 (12%) moderate or severely wasted, and 106 (6%) with elevated weight-to-height (W:H) ratio. Moderate or severe wasting (Adjusted Odds Ratio [AOR] 1.9; 95% Confidence Interval [CI] 1.3, 2.7) and elevated W:H ratio (AOR 1.6; CI 1.1, 2.6) were independent risk factors for wait-list mortality. Among 1,167 patients who underwent HTx, 87% (n=1,016) survived 1-year post-HTx. Pre-transplant nutritional status was not significantly associated with the need for early reoperation, dialysis, incidence of infection, stroke, rejection prior to hospital discharge, or 1-year mortality. Conclusions Moderate or severe wasting and elevated W:H ratio by Waterlow criteria are independent risk factors for wait-list mortality in patients

Abstract 6072: Waitlist Mortality for Infants Awaiting Heart Transplantation in the United States in the Current Era: Analysis of Data from the United Network for Organ Sharing

BACKGROUND UNOS (United Network for Organ Sharing) data suggest that of all pediatric transplant candidates, infants awaiting heart transplantation face the highest waitlist mortality. We sought to determine the mortality rate for waitlisted infants in the current era and to identify the risk factors associated with waitlist mortality. METHODS In this multi-center cohort study using the US Scientific Registry of Transplant Recipients, we analyzed all infants &lt;12 months of age listed for first heart transplant between January 1999 and July 2006. Clinical and demographic characteristics were recorded at the time of listing. Multivariate logistic regression modeling was used to identify predictors of waitlist mortality. RESULTS In this six year period, 1133 patients less than 12 months of age were identified with a median age of 1 month (IQR 0 to 5 mo) and median weight of 4.0 kg (IQR 3.2 to 5.6 kg). 516 (45%) were female, 438 (39%) were non-white, 724 (64%) had congenital heart disease (CHD) and 910 (80%) were listed status 1A. Overall, 250 (22%) died while waiting including 179 (72%) listed at age &lt;3 mo, 190 (76%) with CHD, 89 (35%) listed on mechanical ventilation, and 68 (27%) on ECMO. In multivariate analysis, risk factors for waitlist mortality (reported as hazard ratio, 95% CI) included age &lt;3 months (1.5, 1.1–2.0), CHD (2.0, 1.5–2.7), ventilator support (2.0, 1.5–2.7), ECMO support (5.0, 3.6 –7.0) and non-white race (1.7, 1.4 –2.2). CONCLUSION Mortality of infants waiting for heart transplantation remains high with a 22% waitlist mortality in the current era. ECMO support, ventilator support, CHD, age less than 3 months, and non-white race were independently associated with waitlist mortality whereas listing status was not. Measures to improve donor availability for this age group and refinements in organ allocation to lower waitlist mortality are urgently needed.