Waiting List Deaths Research Articles

The Lung Allocation Score Remains Inequitable for Patients with Pulmonary Arterial Hypertension, Even after the 2015 Revision.

Rationale: The lung allocation score (LAS) was revised in 2015 to improve waiting list mortality and rate of transplant for patients with pulmonary arterial hypertension (PAH). Objectives: We sought to determine if the 2015 revision achieved its intended goals. Methods: Using the Standard Transplant Analysis and Research file, we assessed the impact of the 2015 LAS revision by comparing the pre- and postrevision eras. Registrants were divided into the LAS diagnostic categories: group A-chronic obstructive pulmonary disease; group B-pulmonary arterial hypertension; group C-cystic fibrosis; and group D-interstitial lung disease. Competing risk regressions were used to assess the two mutually exclusive competing risks of waiting list death and transplant. Cumulative incidence plots were created to visually inspect risks. Measurements and Main Results: The LAS at organ matching increased by 14.2 points for registrants with PAH after the 2015 LAS revision, the greatest increase among diagnostic categories (other LAS categories: Δ, -0.9 to +2.8 points). Before the revision, registrants with PAH had the highest risk of death and lowest likelihood of transplant. After the 2015 revision, registrants with PAH still had the highest risk of death, now similar to those with interstitial lung disease, and the lowest rate of transplant, now similar to those with chronic obstructive pulmonary disease. Conclusions: Although the 2015 LAS revision improved access to transplant and reduced the risk of waitlist death for patients with PAH, it did not go far enough. Significant differences in waitlist mortality and likelihood of transplant persist.

314.1: Response to a Pandemic: The Fall and Rise of Kidney Transplantation in the United States

Background: Following the outbreak of COVID-19 in the United States, the number of kidney waitlist additions and living-donor and deceased-donor kidney transplants (LDKT/DDKT) decreased substantially but began recovering within a few months. Since then, there have been several additional waves of infection, most notably, the Delta and current Omicron surge beginning in August and December 2021, respectively. By 1/12/2022, the Omicron surge peaked at 802,699 confirmed new cases, compared to a pre-Omicron peak of 251,772 confirmed new cases on 1/8/2021, demonstrating an immense disease burden on the American population that could have been enough to disrupt transplant practices. Methods: Using data from the Scientific Registry of Transplant Recipients (SRTR), we compared observed waitlist registrations, waitlist mortality, waitlist removal, LDKT, and DDKT in the United States over four distinct pandemic waves to expected events based on calculations from pre-epidemic and non-wave pandemic data, while accounting for seasonality and secular trends. Four distinct time periods/waves of high COVID-19 incidence in the United States were identified for analysis. Wave 1 was defined March 15, 2020 – May 31, 2020; Wave 2 was defined December 1, 2020 – January 31, 2021; Wave 3 was defined August 1, 2021 – September 30, 2021; and Wave 4 was defined December 1, 2021 – January 31, 2022. Waves 1, 2, 3, and 4 were referred to as the Initial, Winter 2021, Delta, and Omicron waves during our analysis. Results: Although the number of daily waitlist additions has been increasing since May 2020, the size of the active waitlist has consistently declined, reaching a minimum of 53,180 on 1/31/2022. The recent Omicron surge knocked LDKT from 12% below expected (IRR = 0.820.880.95) during the Delta wave to 34% below expected (IRR = 0.610.660.71). DDKT, in contrast, was relatively unaffected by the Omicron wave (IRR = 0.830.870.91 and 0.820.850.89 during the Delta and Omicron waves, respectively). Waitlist death declined from 20% above expected (IRR = 1.111.201.30) during Delta to 19% below expected (IRR = 0.740.810.89) during Omicron, whereas waitlist removal remained at expected levels throughout both (IRR = 0.951.041.13 and 0.991.081.18 during Delta and Omicron, respectively). Note, this was the first time that an outcome returned to expected levels since the start of the pandemic. Conclusions: The Omicron wave brought substantial declines in DDKT and LDKT that have not been seen since the Initial wave. Due to vaccine mandates in place at many transplant centers across the nation, the American SRTR population now has high levels of vaccination including high levels of second and third booster shots. Hence, despite the Omicron wave’s exceptionally high COVID-19 infection incidence in the American national cohort, there was no increase in waitlist mortality, likely due to vaccination.Ben-Dov family. K24AI144954 from National Institute of Allergy and Infectious Diseases (NIAID). K01DK101677 from National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).

Waitlist mortality in patients with autoimmune liver diseases

Introduction and ObjectivesAutoimmune liver diseases such as autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis are the primary indication for ∼24% of total liver transplants. The liver transplant allocation system is currently based upon the Model for End-Stage Liver Disease and it often underestimates the severity of autoimmune liver diseases. We aim to compare the rate of adverse waitlist removal among patients with all autoimmune liver diseases and other indications for liver transplant in the Model for End-Stage Liver -Na era. Materials and MethodsUsing the United Network for Organ Sharing database, we identified all patients listed for liver transplant from 2016 to 2019. The outcome of interest was waitlist survival defined as the composite outcome of death or removal for clinical deterioration. Competing risk analysis was used to evaluate the waitlist survival. ResultsPatients with autoimmune hepatitis had a higher risk of being removed from the waitlist for death or clinical deterioration (SHR 1.37, 95% CI 1.08–1.72; P<0.007), followed by primary biliary cholangitis (SHR 1.34, 95% CI 1.07–1.68; P<0.011). ConclusionsHigh waitlist death or removal for clinical deterioration was observed in patients with PBC and AIH when compared to other etiologies. It may be useful to reassess the process of awarding MELD exception points to mitigate such disparity.

Prognosis value of Forrester's classification in advanced heart failure patients awaiting heart transplantation.

The value of Forrester's perfusion/congestion profiles assessed by invasive catheter evaluation in non-inotrope advanced heart failure patients listed for heart transplant (HT) is unclear. We aimed to assess the value of haemodynamic evaluation according to Forrester's profiles to predict events on the HT waitlist. All non-inotrope patients (n=837, 79% ambulatory at listing) registered on the French national HT waiting list between 1 January 2013 and 31 December 2019 with right heart catheterization (RHC) were included. The primary outcome was a combined criteria of waitlist death, delisting for aggravation, urgent HT or left ventricular assist device implantation. Secondary outcome was waitlist death. The 'warm-dry', 'cold-dry', 'warm-wet', and 'cold-wet' profiles represented 27%, 18%, 27%, and 28% of patients, respectively. At 12months, the respective rates of primary outcome were 15%, 17%, 25%, and 29% (P=0.008). Taking the 'warm-dry' category as reference, a significant increase in the risk of primary outcome was observed only in the 'wet' categories, irrespectively of 'warm/cold' status: hazard ratios, 1.50; 1.06-2.13; P=0.024 in 'warm-wet' and 1.77; 1. 25-2.49; P=0.001 in 'cold-wet'. Haemodynamic assessment of advanced HF patients using perfusion/congestion profiles predicts the risk of the combine endpoint of waitlist death, delisting for aggravation, urgent heart transplantation, or left ventricular assist device implantation. 'Wet' patients had the worst prognosis, independently of perfusion status, thus placing special emphasis on the cardinal prominence of persistent congestion in advanced HF.

Prognosis of Advanced Heart Failure Patients according to Their Hemodynamic Profile Based on the Modified Forrester Classification.

Introduction: Heart transplantation (HT) remains the gold-standard treatment but is conditioned by organ shortage. This study aimed to evaluate the value of Forrester classification and determine which congestion criteria had the best prognostic value to predict cardiorenal events on heart transplant waiting list. Methods and results: One hundred consecutive patients (54 years old, 72% men) with available right heart catheterization (RHC) listed in our center for HT between 2014 and 2019 were included. Cardiac catheterization measurements were obtained at the time of HT listing evaluation. Patients were classified according to perfusion and congestion status in four groups: “warm and dry”, “warm and wet”, “cold and dry”, and “cold and wet”. pWet was used to classify patients with pulmonary congestion and sWet for systemic congestion. The primary endpoint was the rate of a composite criteria of cardiogenic shock, acute kidney injury, and acute heart failure. Secondary endpoint was the incidence of waitlist death, emergency HT, or left ventricular assist device (LVAD) implantation at 12 months evaluated by Kaplan–Meier curves and log-rank test. Only Forrester classification according to systemic congestion was associated with the primary composite endpoint (p = 0.011), while patients’ profile according to pulmonary congestion was not (p = 0.331). Similarly, only the Forrester classification according to systemic congestion predicted waitlist death, emergency HT, or LVAD implantation at 12 months, with p = 0.010 and p = 0.189 for systemic and pulmonary congestion, respectively. Moreover, systemic congestion was the main driver of cardiorenal events on waitlist. Conclusions: Forrester classification according to systemic congestion is associated with cardiorenal outcomes in patients listed for heart transplant and the risk of waitlist death, emergency HT, or LVAD implantation at 12 months.

Aortic stenosis post-COVID-19: a mathematical model on waiting lists and mortality

ObjectivesTo provide estimates for how different treatment pathways for the management of severe aortic stenosis (AS) may affect National Health Service (NHS) England waiting list duration and associated mortality.DesignWe constructed...

Primary Liver Transplantation vs. Transplant after Kasai Portoenterostomy for Infants with Biliary Atresia.

Introduction: Primary liver transplants (pLT) in patients with biliary atresia (BA) are infrequent, since most babies with BA undergo a prior Kasai portoenterostomy (KPE). This study compared transplant outcomes in children with BA with or without a prior KPE. We hypothesized that pLT have less morbidity and better outcomes compared to those done after a failed KPE. Methods: A retrospective review of patients with BA transplanted at our institution was performed. Patients were included if they received a pLT or if they were transplanted less than 2 years from KPE. Outcomes were compared between those groups. Comparisons were also made based on era (early: 1997–2008 vs. modern: 2009–2020). p < 0.05 was considered significant. Results: Patients who received a pLT were older at diagnosis (141.5 ± 46.0 vs. KPE 67.1 ± 25.5 days, p < 0.001). The time between diagnosis and listing for transplant was shorter in the pLT group (44.5 ± 44.7 vs. KPE 140.8 ± 102.8 days, p < 0.001). In the modern era, the calculated PELD score for the pLT was significantly higher (23 ± 8 vs. KPE 16 ± 8, p = 0.022). Two waitlist deaths occurred in the KPE group (none in pLT, p = 0.14). Both the duration of transplant surgery and transfusion requirements were similar in both groups. There was a significant improvement in graft survival in transplants after KPE between eras (early era 84.3% vs. modern era 97.8%, p = 0.025). The 1-year patient and graft survival after pLT was 100%. Conclusions: Patient and graft survival after pLT are comparable to transplants after a failed KPE but pLT avoids a prior intervention. There was no significant difference in pre- or peri-transplant morbidity between groups other than wait list mortality. A multicenter collaboration with more patients may help demonstrate the potential benefits of pLT in patients predicted to have early failure of KPE.

Outcomes of extracorporeal membrane oxygenation following the 2018 adult heart allocation policy.

BackgroundThe purpose of the study was to characterize changes in waitlist and post-transplant outcomes of extracorporeal membrane oxygenation (ECMO) patients bridged to heart transplantation under the 2018 adult heart allocation policy.MethodsAll adult patients listed for isolated heart transplantation from August 2016 to December 2020 were identified using the United Network for Organ Sharing database. Patients were stratified into Eras (Era 1 and Era 2) centered around the policy change on October 18, 2018. Competing risk regression was used to evaluate waitlist death or deterioration across Eras. Cox proportional hazards models were used to determine associations between use of ECMO and 1-year post-transplant mortality within each Era.ResultsOf 8,902 heart transplants included in analysis, 339 (3.8%) were bridged with ECMO (Era 2: 6.1% vs Era 1: 1.2%, P<0.001). Patients bridged with ECMO in Era 2 were less frequently female (26.0% vs 42.0%, P = 0.02) and experienced shorter waitlist times (5 vs 11 days, P<0.001) along with a lower likelihood of waitlist death or deterioration (subdistribution hazard ratio, 0.45, 95% confidence interval, CI, 0.30–0.68, P<0.001) compared to those in Era 1. Use of ECMO was associated with increased post-transplant mortality at 1-year compared to all other transplants in Era 1 (hazard ratio 3.78, 95% CI 1.88–7.61, P < 0.001) but not Era 2.ConclusionsPatients bridged with ECMO in Era 2 experience improved waitlist and post-transplant outcomes compared to Era 1, giving credence to the increased use of ECMO under the new allocation policy.

The Evolution of the MELD Score and Its Implications in Liver Transplant Allocation: A Beginner's Guide for Trainees.

The Evolution of the MELD Score and Its Implications in Liver Transplant Allocation: A Beginner's Guide for Trainees.

Use of neural network models to predict liver transplantation waitlist mortality.

Current liver transplantation (LT) organ allocation relies on Model for End-Stage Liver Disease-sodium scores to predict mortality in patients awaiting LT. This study aims to develop neural network (NN) models that more accurately predict LT waitlist mortality. The study evaluates patients listed for LT between February 27, 2002, and June 30, 2021, using the Organ Procurement and Transplantation Network/United Network for Organ Sharing registry. We excluded patients listed with Model for End-Stage Liver Disease (MELD) exception scores and those listed for multiorgan transplant, except for liver-kidney transplant. A subset of data from the waiting list was used to create a mortality prediction model at 90days after listing with 105,140 patients. A total of 28 variables were selected for model creation. The data were split using random sampling into training, validation, and test data sets in a 60:20:20 ratio. The performance of the model was assessed using area under the receiver operating curve (AUC-ROC) and area under the precision-recall curve (AUC-PR). AUC-ROC for 90-day mortality was 0.936 (95% confidence interval [CI], 0.934-0.937), and AUC-PR was 0.758 (95% CI, 0.754-0.762). The NN 90-day mortality model outperformed MELD-based models for both AUC-ROC and AUC-PR. The 90-day mortality model specifically identified more waitlist deaths with a higher recall (sensitivity) of 0.807 (95% CI, 0.803-0.811) versus 0.413 (95% CI, 0.409-0.418; p<0.001). The performance metrics were compared by breaking the test data set into multiple patient subsets by ethnicity, gender, region, age, diagnosis group, and year of listing. The NN 90-day mortality model outperformed MELD-based models across all subsets in predicting mortality. In conclusion, organ allocation based on NN modeling has the potential to decrease waitlist mortality and lead to more equitable allocation systems in LT.

Trends In Waitlist And Post-transplant Outcomes After Heart Transplantation In The United States: Analysis OfUNOS Database 1991-2019

<h3>Background</h3> The landscape of heart transplantation (HT) has changed significantly with respect to patient selection, surgical techniques, and patient outcomes. We sought to investigate temporal trends in patient characteristics, waitlist and post-transplant outcomes after HT in the U.S. <h3>Methods</h3> We queried the national database of the United Network of Organ Sharing (UNOS) to identify adults listed for HT in the U.S. between 1991 and 2019. Patients were divided into four eras based on the three time points in which changes were made to the patient selection/allocation policy (1999, 2006, and 2018), and patient characteristics as well as waitlist and post-transplant outcomes were evaluated for each era. <h3>Results</h3> : Between 1991 and 2019, a total of 95,179 patients were added to the waitlist for HT in the U.S. Compared to era 1, patients listed in era 4 were older (mean age: 52.4 years), more female (27.6%) and ethnic minorities (40%), and with higher-risk comorbidities (28.8% diabetes, 35.6% obese). Over the study period, there were 22,070 waitlist deaths and 61,687 transplants. Compared to the preceding era, there was significant decrease in waitlist mortality in the last 2 eras (e.g., sub-hazard ratio for era 4 vs era 3=0.37, 95% CI=0.32-0.44). For each year, only 27.1% to 40.5% of those on the waitlist were transplanted. Among those who were transplanted, there was increase in the rates of in-hospital stroke (2.8% in era 1 to 3.7% in era 4), renal failure requiring dialysis (7.2% to 17.1%), and hospital length of stay (14 to 17 days), p-values<0.001 for all. However, this has not negatively impacted short-term survival when compared to the preceding era (1-year graft survival=89.7% in era 4). Based on a projection model, we predict a 47% increase in living adult heart transplant recipients to to 44,366 in 2040. <h3>Conclusion</h3> : Although the transplant volume has increased, the wide supply-demand gap persisted. The changes in allocation policy achieved their primary objective of reducing waitlist mortality.

Effects of Blood Group and ABO Compatibility on Lung Transplant Waitlist and Post-Transplant Outcomes

PurposeBlood group O individuals are universal donors, but O recipients are limited to O donors. This constraint combined with the current lung allocation system places O recipients at a hypothetical disadvantage. This study evaluates waitlist outcomes, post-transplant outcomes, and overall survival from time of listing by blood group.MethodsLung transplant candidates from 2/2015 - 2/2019 were identified from the Scientific Registry of Transplant Recipients. A Fine and Gray model adjusted for OPO region, height, sex, and LAS was used to determine the competing risk for waitlist mortality or transplant by blood group and a model adjusted for LAS at transplant used to determine the competing risk for post-transplant mortality. A Cox proportional hazards regression model utilizing a time-varying covariate of transplant and adjusted for the above was used to determine the adjusted risk from listing to death by blood group. Unadjusted outcomes were visualized using Kaplan-Meir curves.ResultsA total of 9,846 candidates were identified, with 8,181 (83%) receiving a lung transplant and 964 (10%) experiencing waitlist death. Blood group A candidates had higher adjusted access to transplant (sHR 1.23, 1.17-1.29) and lower waitlist mortality (sHR 0.77, CI 0.66-0.89) (Fig 1a). AB candidates had a higher adjusted access to transplant (sHR 1.24, CI 1.1-1.4). There was no difference in the adjusted risk for post-transplant death by blood type (Fig 1b). There was no significant difference in mortality from time of listing across blood groups (Fig 1c) and in graft failure or post-transplant mortality by ABO compatibility.ConclusionTransplant equity varies across blood groups with significant differences in adjusted access to transplant and waitlist mortality by blood group. Despite this, post-transplant survival and survival from the time of listing are similar across blood groups. These results support the need to reconsider allocation schemas to mitigate blood group waitlist inequalities. Blood group O individuals are universal donors, but O recipients are limited to O donors. This constraint combined with the current lung allocation system places O recipients at a hypothetical disadvantage. This study evaluates waitlist outcomes, post-transplant outcomes, and overall survival from time of listing by blood group. Lung transplant candidates from 2/2015 - 2/2019 were identified from the Scientific Registry of Transplant Recipients. A Fine and Gray model adjusted for OPO region, height, sex, and LAS was used to determine the competing risk for waitlist mortality or transplant by blood group and a model adjusted for LAS at transplant used to determine the competing risk for post-transplant mortality. A Cox proportional hazards regression model utilizing a time-varying covariate of transplant and adjusted for the above was used to determine the adjusted risk from listing to death by blood group. Unadjusted outcomes were visualized using Kaplan-Meir curves. A total of 9,846 candidates were identified, with 8,181 (83%) receiving a lung transplant and 964 (10%) experiencing waitlist death. Blood group A candidates had higher adjusted access to transplant (sHR 1.23, 1.17-1.29) and lower waitlist mortality (sHR 0.77, CI 0.66-0.89) (Fig 1a). AB candidates had a higher adjusted access to transplant (sHR 1.24, CI 1.1-1.4). There was no difference in the adjusted risk for post-transplant death by blood type (Fig 1b). There was no significant difference in mortality from time of listing across blood groups (Fig 1c) and in graft failure or post-transplant mortality by ABO compatibility. Transplant equity varies across blood groups with significant differences in adjusted access to transplant and waitlist mortality by blood group. Despite this, post-transplant survival and survival from the time of listing are similar across blood groups. These results support the need to reconsider allocation schemas to mitigate blood group waitlist inequalities.

The Lung Allocation Score Remains Inequitable for Patients with PAH, Even After the 2015 Revision

<h3>Purpose</h3> The 2015 LAS revision intended to improve waitlist mortality and transplant rate for patients with pulmonary arterial hypertension (PAH). We sought to determine if the revision achieved its goals. <h3>Methods</h3> Using the OPTN STAR file, we analyzed the 15,807 registrants in the 3-year period before and after the revision. Registrants were divided into the LAS diagnostic categories: Group A-COPD; Group B-PAH; Group C-CF; & Group D-IPF. Competing risk regressions assessed the mutually exclusive competing risks of waitlist death and transplantation. Models were adjusted for age, gender, race, height, transplant type, and blood type. Cumulative incidence plots were created to visually inspect risks. <h3>Results</h3> Amongst the combined cohort, risk of waitlist death was lower post revision (sHR: 0.84, 95%CI: 0.78, 0.91), and likelihood of transplant was higher (sHR: 1.16, 95%CI: 1.12, 1.21). When stratified by LAS Category, risk of waitlist death remained similar for all diagnoses post revision, except in PAH, where risk of waitlist death improved (sHR: 0.57, 95%CI: 0.50, 0.85). Likelihood of transplant improved for all diagnoses post revision (all p<0.001). Prior to the revision, registrants with PAH had the highest risk of waitlist death and lowest likelihood of transplant (Figure). After the 2015 revision, registrants with PAH continued to have the highest risk of death, similar to those with IPF, who had the highest rate of transplant (sHR for IPF relative to PAH: 0.95, 95%CI: 0.67, 1.33). Registrants with PAH also continued to have the lowest rate of transplant, and registrants with COPD, which had the lowest risk of waitlist death, still tended to be transplanted at a higher rate than those with PAH (sHR for COPD relative to PAH 1.14, 95%CI: 0.99, 1.31). <h3>Conclusion</h3> Despite improving access to transplantation and risk of waitlist death for patients with PAH, the 2015 LAS revision did not go far enough, as patients with PAH still have the highest rate of waitlist death and lowest rate of transplant.

The Regional Impact of the 2018 United States Heart Allocation System Change

Purpose In October 2018, the US Organ Procurement and Transplantation Network (OPTN) implemented a change in the donor heart allocation policy, with priority given to those with temporary mechanical circulatory support and expanded regional sharing. The purpose of the current study was to examine changes in waitlist/transplant outcomes across the US with the policy change, stratified by geographic region. Methods Retrospective analysis was performed of adult patients listed for heart transplant between January 2016-July 2021 as identified in the OPTN database. Patients were grouped by era according to initial listing date before or after October 18, 2018 as well as OPTN region. Competing outcomes regression was performed for waitlist death, transplant, or delisting utilizing the method of Fine and Gray, along with cause-specific hazard modeling. Models were censored at 3y. Results During the study period, 23,146 patients were listed, with 11,494 prior to (Era 1, 49.7%) and 11,652 after system change (Era 2, 50.3%). IABP and ECMO usage amongst waitlist patients increased in Era 2 across all regions (all p<0.05). Waitlist mortality improved in all regions except the South (Region 3 and 4) and Northwest (Regions 6-8, p>0.10). Odds of transplantation increased in all regions to varying degrees. However, amongst patients with LVAD support, waitlist mortality was only improved in Region 2 (Mid-Atlantic, p=0.016) and Region 5 (Southwest, p=0.041), with a commensurate increase in transplantation in Region 5 (SHR 1.48 [1.22-1.80], p<0.001). Among those transplanted, organ distance increased by >80 mi in all regions except Region 1 (Northeast), with increases in ischemic time in all regions except Region 1 (p=0.358). Conclusion The implementation of the new allocation system broadly decreased waitlist mortality and improved rates of transplantation, though effects were dependent on geographic region. Continued examination of listing practices and organ allocation with respect towards geographic variation is warranted. In October 2018, the US Organ Procurement and Transplantation Network (OPTN) implemented a change in the donor heart allocation policy, with priority given to those with temporary mechanical circulatory support and expanded regional sharing. The purpose of the current study was to examine changes in waitlist/transplant outcomes across the US with the policy change, stratified by geographic region. Retrospective analysis was performed of adult patients listed for heart transplant between January 2016-July 2021 as identified in the OPTN database. Patients were grouped by era according to initial listing date before or after October 18, 2018 as well as OPTN region. Competing outcomes regression was performed for waitlist death, transplant, or delisting utilizing the method of Fine and Gray, along with cause-specific hazard modeling. Models were censored at 3y. During the study period, 23,146 patients were listed, with 11,494 prior to (Era 1, 49.7%) and 11,652 after system change (Era 2, 50.3%). IABP and ECMO usage amongst waitlist patients increased in Era 2 across all regions (all p<0.05). Waitlist mortality improved in all regions except the South (Region 3 and 4) and Northwest (Regions 6-8, p>0.10). Odds of transplantation increased in all regions to varying degrees. However, amongst patients with LVAD support, waitlist mortality was only improved in Region 2 (Mid-Atlantic, p=0.016) and Region 5 (Southwest, p=0.041), with a commensurate increase in transplantation in Region 5 (SHR 1.48 [1.22-1.80], p<0.001). Among those transplanted, organ distance increased by >80 mi in all regions except Region 1 (Northeast), with increases in ischemic time in all regions except Region 1 (p=0.358). The implementation of the new allocation system broadly decreased waitlist mortality and improved rates of transplantation, though effects were dependent on geographic region. Continued examination of listing practices and organ allocation with respect towards geographic variation is warranted.

Discussion summary: MELD 3.0: The Model for End-Stage Liver Disease Updated for the Modern Era

BACKGROUND &amp; AIMS: The Model for End-Stage Liver Disease (MELD) has been established as a reliable indicator of shortterm survival in patients with end-stage liver disease. The current version (MELDNa), consisting of the international normalized ratio and serum bilirubin, creatinine, and sodium, has been used to determine organ allocation priorities for liver transplantation in the United States. The objective was to optimize MELD further by taking into account additional variables and updating coefficients with contemporary data. METHODS: All candidates registered on the liver transplant wait list in the US national registry from January 2016 through December 2018 were included. Uni- and multivariable Cox models were developed to predict survival up to 90 days after wait list registration. Model fit was tested using the concordance statistic (C-statistic) and reclassification, and the Liver Simulated Allocation Model was used to estimate the impact of replacing MELDNa with the new model. RESULTS: The final multivariable model was characterized by (1) additional variables of female sex and serum albumin, (2) interactions between bilirubin and sodium and between albumin and creatinine, and (3) an upper bound for creatinine at 3.0 mg/dL. The final model (MELD 3.0) had better discrimination than MELDNa (C-statistic, 0.869 vs 0.862; P &lt; .01). Importantly, MELD 3.0 correctly reclassified a net of 8.8% of decedents to a higher MELD tier, affording them a meaningfully higher chance of transplantation, particularly in women. In the Liver Simulated Allocation Model analysis, MELD 3.0 resulted in fewer wait list deaths compared to MELDNa (7788 vs 7850; P= .02). CONCLUSION: MELD 3.0 affords more accurate mortality prediction in general than MELDNa and addresses determinants of wait list outcomes, including the sex disparity.

Human leukocyte antigen antibody sensitization, lung transplantation, and health equity

Women with advanced lung disease, particularly Black and Hispanic women, are more likely than other patients to have anti-human leukocyte (HLA) antibodies against potential donors. Sensitized patients, especially those who are highly sensitized, are less likely to be listed for lung transplant or to be considered candidates for mechanical circulatory support. They are also at higher risk for waitlist death. Institutional variability in approach to HLA antibody screening and pre-transplant management creates barriers to transplant that disproportionately impact Black and Hispanic women. At the same time, our understanding of the clinical significance of pre-transplant antibodies lags behind the sophistication of our screening assays. The lack of national data on pre- and post-transplant HLA antibody characteristics hinders research into strategies to mitigate concerns about these antibodies and to improve access to lung transplant among sensitized patients. Ongoing work should be done to identify clinically higher risk antibodies, to develop better strategies for safely crossing antibodies at the time of transplant, and to model changes in lung allocation to give priority to sensitized patients for a HLA antibody-antigen compatible donors. These priorities mandate a commitment to collaborative, multicenter research and to real time translation of results to clinical practice and allocation policy.

Recovery With Temporary Mechanical Circulatory Support While Waitlisted for Heart Transplantation

BackgroundThe 2018 U.S. heart allocation system offers an accelerated pathway for heart transplantation to the most urgent patients. ObjectivesThis study sought to determine whether the new allocation system resulted in lower likelihood of candidate recovery. MethodsAdult patients waitlisted for heart transplantation with temporary mechanical circulatory support at the time of initial listing between 2010 and 2020 in the United Network for Organ Sharing registry were included. Competing events of heart transplantation, waitlist death or delisting for deteriorating condition, and delisting for improved condition (candidate recovery) were analyzed in the new vs old heart allocation system. ResultsA total of 688 patients were waitlisted with venoarterial extracorporeal membrane oxygenation or a surgical nondischargeable biventricular assist device (status 1 or old 1A). Overall, 2,237 patients were waitlisted with an intra-aortic balloon pump, a percutaneous left ventricular assist device (LVAD), or a surgical nondischargeable LVAD (status 2 or old 1A). Patients waitlisted with venoarterial extracorporeal membrane oxygenation or a nondischargeable biventricular assist device had significantly shorter median waitlist times (5 vs 31 days), higher incidence for cardiac transplantation (81.5% vs 43.0%), and lower incidence of candidate recovery (1.5% vs 7.9%) in the new vs old heart allocation system (all P < 0.05). Patients waitlisted with an intra-aortic balloon pump or percutaneous or a nondischargeable LVAD also had significantly shorter median waitlist times (8 vs 35 days), higher incidence of transplantation (88.9% vs 64.9%), and lower incidence of candidate recovery (0.2% vs 1.6%) in the new vs old heart allocation system (all P < 0.05). ConclusionsCurrent practice of the new allocation system may not offer select temporary mechanical circulatory support patients the opportunity and adequate time to recover to the point of waitlist removal. Further research will determine which patients would benefit from urgent transplantation vs recovery strategy.

Liver transplant in children and adults with cystic fibrosis: Impact of growth failure and nutritional status

Nutritional status is known to strongly predict health outcomes in people with cystic fibrosis (CF), but the prevalence of and consequences for CF children with growth failure and underweight CF adults on the liver transplant (LT) waitlist has not been delineated. We utilized UNOS registry data from 2003 to 2017 to investigate the impact of growth failure and underweight on outcomes in liver transplant candidates with CF. Almost 1 in 3 children and adults with CF had growth failure or were underweight, respectively, at listing. Body mass index under-estimated growth failure compared to height and weight z-scores for children. In multivariate analysis of children, growth failure (HR 2.1, 95% CI 1.7-2.6), and CF (HR 2.7, 95% CI 1.6-4.6, vs. Non-CF) were independent risk factors for waitlist death among children; having both increased death risk almost fourfold (SHR 3.88, 95% CI 1.42-10.58). However, among children who did receive a LT, CF was not associated with death within 1-year post-LT. Underweight adult CF candidates were less likely to receive LT, again suggesting the importance of nutritional evaluation and early intervention in this at-risk cohort.

An Intention-to-treat View of Lung Transplantation for Interstitial Lung Disease: Successful Strategies to Minimize Waiting List and Posttransplant Mortality.

Access to lung transplantation (LTx) and rates of waiting list and posttransplant mortality for patients with interstitial lung disease (ILD) remain problematic. We evaluated the outcomes of ILD patients listed for LTx at our institution. Between 2012 and 2018, adult patients with ILD were listed and transplanted from a donor-pool that included extended criteria and donation after circulatory-determined death donors. Patients were categorized as experiencing 1 of 4 competing events: transplant, waitlist death, delisting, or alive on waitlist. Multivariable competing risk regression analysis was performed to determine predictors of waitlist death/delisting. Posttransplant survival was analyzed using Kaplan-Meier methods. Among 187 patients listed, 82% (153 of 187) underwent LTx (median time-to-transplant, 2.0 mo), whereas 16% (30 of 187) died or were delisted (median time-to-event, 1.6 mo). At 90 d, 6 mo, and 12 mo after listing, 51%, 63%, and 78% of patients had been transplanted, whereas 10%, 14%, and 16% had died or were delisted. Multivariable predictors of waitlist death/delisting were: blood group O compared to A (subdistribution hazard ratio [SHR]: 6.43, P < 0.001), shorter height (per 1 cm, SHR: 1.11, P < 0.001), hospitalization at listing (SHR: 3.98, P = 0.002), and reduced 6-min-walk test distance (per 50 m, SHR: 1.28, P = 0.001). Among LTx recipients, 24% (36 of 153) underwent single LTx. Donor lungs were 58% (88 of 153) extended-criteria, inclusive of 24% (37 of 153) circulatory-determined death. Ninety-day and 1-, 3-, and 5-y retransplant free survival were 97% ± 1%, 92% ± 2%, 81% ± 4%, and 69% ± 6%. Patients with ILD require a rapid transit to LTx after listing. Despite this, the vast majority of ILD patients in this study reached LTx with excellent early and midterm outcomes.

Impact of Obesity on Heart Transplantation Outcomes.

BackgroundPatients with obesity and advanced heart failure face unique challenges on the path to heart transplantation. There are limited data on waitlist and transplantation outcomes in this population. We aimed to evaluate the impact of obesity on heart transplantation outcomes, and to investigate the effects of the new organ procurement and transplantation network allocation system in this population.Methods and ResultsThis cohort study of adult patients listed for heart transplant used the United Network for Organ Sharing database from January 2006 to June 2020. Patients were stratified by body mass index (BMI) (18.5–24.9, 25–29.9, 30–34.9, 35–39.9, and 40–55 kg/m2). Recipient characteristics and donor characteristics were analyzed. Outcomes analyzed included transplantation, waitlist death, and posttransplant death. BMI 18.5 to 24.9 kg/m2 was used as the reference compared with progressive BMI categories. There were 46 645 patients listed for transplantation. Patients in higher BMI categories were less likely to be transplanted. The lowest likelihood of transplantation was in the highest BMI category, 40 to 55 kg/m2 (hazard ratio [HR], 0.19 [0.05–0.76]; P=0.02). Patients within the 2 highest BMI categories had higher risk of posttransplantation death (HR, 1.29; P<0.001 and HR, 1.65; P<0.001, respectively). Left ventricular assist devices among patients in obese BMI categories decreased after the allocation system change (P<0.001, all). After the change, patients with obesity were more likely to undergo transplantation (BMI 30–35 kg/m2: HR, 1.31 [1.18–1.46], P<0.001; BMI 35–55 kg/m2: HR, 1.29 [1.06–1.58]; P=0.01).ConclusionsThere was an inverse relationship between BMI and likelihood of heart transplantation. Higher BMI was associated with increased risk of posttransplant mortality. Patients with obesity were more likely to undergo transplantation under the revised allocation system.