Post-transplant Mortality Research Articles

Increasing waiting times for status 2 patients in new United Network for Organ Sharing allocation system: Impact on waitlist and posttransplant outcomes

ObjectiveSince the heart transplant allocation policy change in 2018, there has been an increase in temporary mechanical circulatory support for Status 2 patients. We sought to examine the temporal pattern of waitlist and posttransplant outcomes for Status 2 patients. MethodsAdult patients in the United Network for Organ Sharing registry who were listed as Status 2 from January 2019 to June 2022 were included. Temporal trends in waitlist time, waitlist events, and posttransplant outcomes were assessed. Probability of transplant or death after being listed was compared over time. Multivariable regression was performed to identify risk factors for mortality after transplant. ResultsA total of 6310 patients were included. From 2019 to 2022, the number of Status 2 patients listed increased from 4.2 to 5.9 per day. Microaxial ventricular assist devices at Status 2 listing increased over time (P < .001). During the study period, median waitlist time (18 days vs 23 days, P < .001) as well as Status 2 days (8 days vs 12 days, P < .001) increased. Waitlist mortality remained stable (5.5%); however, probability of transplant within 90 days of Status 2 listing progressively declined (P < .001). Finally, longer waitlist duration was independently associated with 30-day posttransplant mortality (odds ratio, 1.01; 95% confidence interval, 1.00-1.01, P = .02). ConclusionsSince the allocation policy change there has been a steady rise in the number of patients listed for Status 2. This has led to increasing waitlist times and lower probability of transplantation for Status 2 patients, which may have negative consequences for posttransplant outcomes.

#3159 IMPACT OF MENTAL ILLNESS ON POST-TRANSPLANTATION OUTCOMES IN NEW ZEALAND: THE ASSET-MH DATA LINKAGE STUDY

Abstract Background and Aims People with severe mental illness are 6 times more likely to develop kidney disease. Mental illness is overrepresented in the kidney failure population. Up to 40% of dialysis patients are affected by depression and anxiety. There is limited understanding of the extent and impact of mental illness on transplant outcomes. We aimed to evaluate the impact mental illness has upon post-transplant outcomes, including graft failure and death in kidney transplant recipients in New Zealand. Method We included all incident kidney transplant recipients in New Zealand, 2006-2019 from the ASSET linked data platform, including Australian and New Zealand Dialysis and Transplant Registry, and national health registries (eg. hospitalisations, prescriptions and mental health services). Presence of mental illness was ascertained based on past use of medications (antipsychotics and antidepressants) and mental health services (community/residential support and inpatient) occurring at least twice over a year. Follow-up was from transplantation until death, graft failure or 31st Dec 2019. We used Cox models to evaluate risk of graft failure or death for mental health users compared to non-mental health users, adjusting for age, sex, calendar year and prior dialysis time. Results We included 1,796 kidney transplant recipients, where 457 (25%) had mental illness comorbidity. Overall, 228 (13%) used medication for mental illness (25 antipsychotics; 203 antidepressants) and 340 (19%) used mental health services (327 community/residential support; 14 inpatient). There were 111 recipients (6%) who had used medications and services for mental illness. There were 42 (9%) graft failures and 34 (7%) deaths among those with mental illness compared to 137 (10%) graft failures and 125 (9%) deaths among those without mental illness. Those with mental illness had the same risk of graft failure compared to others (p = 0.17), regardless of whether they used antidepressants (HR: 1.52, 95%CI: 0.93-2.48, p = 0.09) or received community/residential support (HR: 1.19, 95%CI: 0.78-1.81, p = 0.42). There were no graft failures among those using antipsychotics or receiving inpatient care. Risk of death increased 3-fold (HR: 3.24, 95%CI: 1.51-6.99, p &amp;lt; 0.01) in those using antipsychotics compared to those without mental illness, but was not increased among those using antidepressants (HR: 0.90, 95%CI: 0.47-1.72, p = 0.74). There was weak evidence for an increased risk of death among those receiving community/residential support (HR: 1.57, 95%CI: 0.99-2.49, p = 0.06) compared to those without mental illness. Risk of death was not significantly associated with those receiving inpatient care (HR: 3.00, 95%CI:0.72-12.42, p = 0.13), although event rates were low. For composite of graft failure or death, those with mental illness had the same risk as those without (p &amp;gt; 0.10), regardless of receiving antipsychotics (HR: 1.77, 95%CI: 0.83-3.75) or antidepressants (HR: 1.23, 95%CI: 0.84-1.82), or community/residential support (HR: 1.37, 95%CI: 1.00-1.87) or inpatient care (HR: 1.41, 95%CI: 0.35-5.71). Conclusion Mental illness comorbidity is common in this setting, with one in ten transplant recipients in New Zealand receiving psychiatric treatment. Antipsychotic use was associated with three times the risk of death. Otherwise, those with mental illness had comparable post-transplant outcomes. There is opportunity for more collaborative psychiatric and transplant services to promote better patient outcomes and reduce post-transplant mortality.

The novel SALT-M score predicts 1-year post-transplant mortality in patients with severe acute-on-chronic liver failure

Twenty-eight-day mortality ranges from 30-90% in patients with acute-on-chronic liver failure grades 2/3 (severe ACLF). Though liver transplantation (LT) has demonstrated a survival benefit, the scarcity of donor organs and uncertainty regarding post-LT mortality among patients with severe ACLF may cause hesitancy. We developed and externally validated a model to predict 1-year post-LT mortality in severe ACLF, called the Sundaram ACLF-LT-Mortality (SALT-M) score, and estimated the median length of stay (LoS) after LT (ACLF-LT-LoS). In 15 LT centers in the US, we retrospectively identified a cohort of patients with severe ACLF transplanted between 2014-2019, followed up to Jan'2022. Candidate predictors included demographics, clinical and laboratory values, and organ failures. We selected predictors in the final model using clinical criteria and externally validated them in two French cohorts. We provided measures of overall performance, discrimination, and calibration. We used multivariable median regression to estimate LoS after adjusting for clinically relevant factors. We included 735 patients, of whom 521 (70.8%) had severe ACLF (120 ACLF-3, external cohort). The median age was 55 years, and 104 with severe ACLF (19.9%) died within 1-year post-LT. Our final model included age >50 years, use of 1/≥2 inotropes, presence of respiratory failure, diabetes mellitus, and BMI (continuous). The c-statistic was 0.72 (derivation) and 0.80 (validation), indicating adequate discrimination and calibration based on the observed/expected probability plots. Age, respiratory failure, BMI, and presence of infection independently predicted median LoS. The SALT-M score predicts mortality within 1-year after LT in patients with ACLF. The ACLF-LT-LoS score predicted median post-LT stay. Future studies using these scores could assist in determining transplant benefits. Liver transplantation (LT) may be the only life-saving procedure available to patients with acute-on-chronic liver failure (ACLF), but clinically instability can augment the perceived risk of post-transplant mortality at 1 year. We developed a parsimonious score with clinically and readily available parameters to objectively assess 1-year post-LT survival and predict median length of stay after LT. We developed and externally validated a clinical model called the Sundaram ACLF-LT-Mortality score in 521 US patients with ACLF with 2 or ≥3 organ failure(s) and 120 French patients with ACLF grade 3. The c-statistic was 0.72 in the development cohort and 0.80 in the validation cohort. We also provided an estimation of the median length of stay after LT in these patients. Our models can be used in discussions on the risks/benefits of LT in patients listed with severe ACLF. Nevertheless, the score is far from perfect and other factors, such as patient's preference and center-specific factors, need to be considered when using these tools.

CARD17: 24 hr Normothermic Ex Vivo Heart Perfusion in Adult Porcine Hearts with Hemofiltration

Introduction: Currently, to successfully transplant a heart, cardiac preservation relies on cold static storage at 5C for up to 6 hours. If hearts are stored at this temperature for a longer duration, their function after transplantation is compromised, increasing post-transplant morbidity and mortality. This time restriction negatively impacts the availability of donor hearts and limits distance and transportation options, optimal cross-matching, and organ assessment, all of which facilitate successful transplantation. Previous studies from our group have demonstrated that: 1) Plasma cross circulation at 1 L/hr from a living paracorporeal sheep allowed for safe normothermic ex vivo heart perfusion (NEVHP) for 3 days, 2) NEVHP for 24 hours is feasible with plasma exchange without a paracorporeal animal, 3) 24-hour NEVHP is also feasible with the addition of hemofiltration (22 kDa filter) and filtration replacement. All studies with up to 24hr of NEVHP were performed using piglet hearts (60±8.8 g) The experiments described in this study were designed to evaluate the efficacy of hemofiltration and filtrate replacement in adult porcine hearts. Methods: We performed 24-hour NEVHP on 5 consecutive hearts (mean weight 263±15.5 g). Following anesthetic induction, sternotomy, cardioplegia administration, explantation, and back-table instrumentation, NEVHP was initiated in beating, resting mode. After 1 hour plasma exchange was performed and hemofiltration was initiated. Heart function parameters and arterial blood gasses were obtained hourly and at termination of prep all hearts were removed from circuit and stored in formalin. Results: All hearts (n=5) were viable at the 24-hour mark. Aortic blood flow was adjusted to maintain coronary artery blood flow at 0.7 mL/min/g. Average LV systolic pressure at the beginning of the prep was 36.6±7.9 mmHg compared to 27±5.5 mmHg at the end. Coronary resistance at the beginning of prep was 0.79±0.10 mmHg/L/min and at the end of prep was 0.93±0.28 mmHg/L/min. Glucose levels averaged 223±13.9 mg/dL and the lactate average at the termination of prep was 2.6±0.3 mmol/L. Conclusions: We successfully perfused adult porcine hearts at normothermic temperatures for 24 hours with results comparable to our pediatric porcine heart model. The next steps in our research are NEVHP evaluation in a working mode using left atrial perfusion, extension of NEVHP preservation beyond 24 hours, and verification of functional status of the ex vivo heart by transplantation after 24 hours on our circuit.

Clinical Outcomes of Adult Fontan-Associated Liver Disease and Combined Heart-Liver Transplantation

BackgroundThe impact of Fontan-associated liver disease (FALD) on post-transplant mortality and indications for combined heart-liver transplant (CHLT) in adult Fontan patients remains unknown. ObjectivesThe purpose of this study was to assess the impact of FALD on post-transplant outcomes and compare HT vs CHLT in adult Fontan patients. MethodsWe performed a retrospective-cohort study of adult Fontan patients who underwent HT or CHLT across 15 centers. Inclusion criteria were as follows: 1) Fontan; 2) HT/CHLT referral; and 3) age ≥16 years at referral. Pretransplant FALD score was calculated using the following: 1) cirrhosis; 2) varices; 3) splenomegaly; or 4) ≥2 paracenteses. ResultsA total of 131 patients (91 HT and 40 CHLT) were included. CHLT recipients were more likely to be older (P = 0.016), have a lower hemoglobin (P = 0.025), require ≥2 diuretic agents pretransplant (P = 0.051), or be transplanted in more recent decades (P = 0.001). Postmatching, CHLT demonstrated a trend toward improved survival at 1 year (93% vs 74%; P = 0.097) and improved survival at 5 years (86% vs 52%; P = 0.041) compared with HT alone. In patients with a FALD score ≥2, CHLT was associated with improved survival (1 year: 85% vs 62%; P = 0.044; 5 years: 77% vs 42%; P = 0.019). In a model with transplant decade and FALD score, CHLT was associated with improved survival (HR: 0.33; P = 0.044) and increasing FALD score was associated with worse survival (FALD score: 2 [HR: 14.6; P = 0.015], 3 [HR: 22.2; P = 0.007], and 4 [HR: 27.8; P = 0.011]). ConclusionsHigher FALD scores were associated with post-transplant mortality. Although prospective confirmation of our findings is necessary, compared with HT alone, CHLT recipients were older with higher FALD scores, but had similar survival overall and superior survival in patients with a FALD score ≥2.

Morbidity and Mortality in Adult Fontan Patients After Heart or Combined Heart-Liver Transplantation

BackgroundAn increasing number of adult Fontan patients require heart transplantation (HT) or combined heart-liver transplant (CHLT); however, data regarding outcomes and optimal referral time remain limited. ObjectivesThe purpose of this study was to define survivorship post-HT/CHLT and predictors of post-transplant mortality, including timing of referral, in the adult Fontan population. MethodsA retrospective cohort study of adult Fontan patients who underwent HT or CHLT across 15 centers in the United States and Canada was performed. Inclusion criteria included the following: 1) Fontan; 2) HT/CHLT referral; and 3) age ≥16 years at the time of referral. Date of “failing” Fontan was defined as the earliest of the following: worsening fluid retention, new ascites, refractory arrhythmia, “failing Fontan” diagnosis by treating cardiologist, or admission for heart failure. ResultsA total of 131 patients underwent transplant, including 40 CHLT, from 1995 to 2021 with a median post-transplant follow-up time of 1.6 years (Q1 0.35 years, Q3 4.3 years). Survival was 79% at 1 year and 66% at 5 years. Survival differed by decade of transplantation and was 87% at 1 year and 76% at 5 years after 2010. Time from Fontan failure to evaluation (HR/year: 1.23 [95% CI: 1.11-1.36]; P < 0.001) and markers of failure, including NYHA functional class IV (HR: 2.29 [95% CI: 1.10-5.28]; P = 0.050), lower extremity varicosities (HR: 3.92 [95% CI: 1.68-9.14]; P = 0.002), and venovenous collaterals (HR: 2.70 [95% CI: 1.17-6.20]; P = 0.019), were associated with decreased post-transplant survival at 1 year in a bivariate model that included transplant decade. ConclusionsIn our multicenter cohort, post-transplant survival improved over time. Late referral after Fontan failure and markers of failing Fontan physiology, including worse functional status, lower extremity varicosities, and venovenous collaterals, were associated with post-transplant mortality.

Effect of the UNOS policy change on rates of rejection, infection, and hospital readmission following heart transplantation

The 2018 adult heart allocation policy soughtto improve waitlist risk stratification, reduce waitlist mortality, and increase organ access. This system prioritized patients at greatest risk for waitlist mortality, especially individuals requiring temporary mechanical circulatory support (tMCS). Posttransplant complications are significantly higher in patients on tMCS before transplantation, and early posttransplant complications impact long-term mortality. We sought to determine if policy change affected early posttransplant complication rates of rejection, infection, and hospitalization. We included all adult, heart-only, single-organ heart transplant recipients from the UNOS registry with pre-policy (PRE) individuals transplanted between November1, 2016, and October 31, 2017, and post-policy (POST) between November1, 2018, and October 31, 2019. We used a multivariable logistic regression analysis to assess the effect of policy change on posttransplant rejection, infection, and hospitalization. Two COVID-19 eras (2019-2020, 2020-2021) were included in our analysis. The majority of baseline characteristics were comparable between PRE and POST era recipients. The odds of treated rejection (p=0.8), hospitalization (p=0.69), and hospitalization due to rejection (p=0.76) and infection (p=0.66) were similar between PRE and POST eras; there was a trend towards reduced odds of rejection (p=0.08). In both COVID eras, there was a clear reduction in rejection and treated rejection with no effect on hospitalization for rejection or infection. Odds of all-cause hospitalization was increased in both COVID eras. The UNOS policy change improves access to heart transplantation for higher acuity patients without increasing early posttransplant rates of treated rejection or hospitalization for rejection or infection, factors which portend risk for long-term posttransplant mortality.

Chronotropic Incompetence after Heart Transplantation Is Associated with Increased Mortality and Decreased Functional Capacity.

The contribution of chronotropic incompetence to reduced exercise tolerance after a heart transplant is well known, but its role as a prognostic marker of post-transplant mortality is unclear. The aim of this study is to examine the relationship between post-transplant heart rate response (HRR) and survival. We performed a retrospective analysis of all adult heart transplant recipients at the University of Pennsylvania between the years 2000 and 2011 who underwent a cardiopulmonary exercise test (CPET) within a year of transplant. Follow-up time and survival status were observed through October 2019, using data merged from the Penn Transplant Institute. HRR was calculated by subtracting the resting HR from the peak exercise HR. The association between HRR and mortality was analyzed using Cox proportional hazard models and Kaplan-Meier analysis. The optimal cut-off point for HRR was generated by Harrell's C statistic. Patients with submaximal exercise tests were excluded, defined by a respiratory exchange ratio (RER) cut-off of 1.05. Of 277 patients with CPETs performed within a year post-transplant, 67 were excluded for submaximal exercise. In the 210 included patients, the mean follow-up time was 10.9 years (Interquartile range (IQR) 7.8-14). Resting HR and peak HR did not significantly impact mortality after adjusting for covariates. In a multivariable linear regression analysis, each 10-beat increase in heart rate response was associated with a 1.3 mL/kg/min increase in peak VO2 and a 48 s increase in the total exercise time. Each beat/min increase in HRR was associated with a 3% reduction in the hazard of mortality (HR 0.97; 95% CI 0.96-0.99, p = 0.002). Using the optimal cut-off point generated by Harrell's C statistic, survival was significantly higher in patients with an HRR > 35 beats/min compared to those with an HRR < 35 beats/min (log rank p = 0.0012). In heart transplant patients, a low HRR is associated with increased all-cause mortality and decreased exercise capacity. Additional studies are needed to validate whether targeting HRR in cardiac rehabilitation may improve outcomes.

Association between skeletal muscle index prior to liver transplantation and 1-year mortality posttransplant.

Liver transplantation is the only curative therapy for end-stage liver disease (ESLD). Sarcopenia is often defined as the loss of muscle quantity (skeletal muscle index [SMI]), but muscle attenuation (MA), a surrogate marker of muscle quality, is also decreased in ESLD. We assessed pre-liver transplant SMI and MA and their association with posttransplant mortality, complications, and length of intensive care unit (ICU) and hospital stay. In 169 consecutive patients with ESLD who underwent a liver transplantation between 2007 and 2014, SMI and MA were measured on computed tomography scans at time of placement on the waiting list for liver transplantation. The primary outcome of interest was 1-year posttransplant mortality. Secondary posttransplantation outcomes of interest were complications within 30 days and length of stay in the ICU > 3 days and in the hospital >3 weeks. Logistic and Cox regression analyses were performed. MA was associated with 1-year posttransplant mortality rate (hazard ratio=0.656, 95% CI=0.464-0.921, P = 0.015). The highest quartile of SMI had a lower odds for the total length of stay in the hospital lasting >3 weeks (odds ratio=0.211, 95% CI=0.061-0.733, P = 0.014). MA was associated with a prolonged ICU stay; this was, however, not statistically significant after adjustment for age, sex, and Model for ESLD score. Lower MA is associated with a longer length of ICU stay and 1-year mortality after liver transplantation, whereas low SMI was associated with a total length of hospital stay.

O050 Utility of ramp test time in patients undergoing assessment for renal transplantation

Abstract Introduction Prior to renal transplant listing, cardiovascular screening is performed to stratify the risk of cardiovascular disease (CVD). During pre-assessment in our centre, patients undergo a ramp test (a timed assessment to walk 130m), which is a rapid and non-invasive method of quantifying exercise tolerance. The purpose of this study is to correlate ramp test time (RTT) with transplant waiting list status, cardiac stress testing, and post-transplant CV events and mortality. Methods Retrospective analysis of patients that underwent pre-assessment. Data collection included patient demographics, history of CVD and diabetes, RTT, ejection fraction and evidence of myocardial ischaemia, transplant list status, any subsequent CV event, and mortality. Three groups were analysed: (1) patients unable to perform the test; (2) RTT≥2mins; (3) RTT≤1min. Results 1508 patients were pre-assessed for transplantation between 2014-2022. Mean RTT was 86 seconds (SD±26 seconds). Patients with RTT&amp;lt;1min were younger with less pre-existing CVD, of whom 93% had normal cardiac stress testing. Over half of the patients who either had RTT &amp;gt;2mins or were unable to perform the test had abnormal cardiac function, with a 3-year mortality of about 30%. Conclusion RTT can be used to assess cardiovascular suitability for transplantation. Patients unable to perform the test are unlikely to be listed for transplantation, with a quarter suffering a CV event post-assessment. In contrast, patients with RTT≤1min are almost all activated with no subsequent CV events. The low rate of CV events or abnormal stress tests in this group may allow early activation without extensive cardiovascular assessment.

Muscle quality determined by computed tomography predicts short-term and long-term survival after liver transplantation

Sarcopenia, the loss of muscle mass and quality, contributes to worse clinical outcome in patients with end-stage liver disease, but its impact on short- and long-term survival remains insufficiently understood. The aim of this study was to evaluate the development of computed tomography (CT) muscle parameters and their impact on short-term and long-term survival after liver transplantation. This retrospective study included patients with liver transplantation between 2011 and 2015 and a pre-transplant CT scan. Clinical characteristics, CT muscle mass and density were assessed pre-transplant, and in available CT scans at short-term (11 months) and long-term follow-up (56 months). Overall, 93/152 (61%) patients (109 male, 55 ± 10 years) suffered from sarcopenia pre-transplant. In short- (n = 50) and long-term follow-up (n = 52) the muscle mass (− 2.65 cm2/m2 95% CI [− 4.52, − 0.77], p = 0.007; − 2.96 cm2/m2 [− 4.7, − 1.23], p = 0.001, respectively), and muscle density (− 3 HU [− 6, − 1], p = 0.007; − 2 HU [− 4, 0], p = 0.069) decreased. Myosteatosis was associated with a higher post-transplant mortality (survival probability: 3 months 72% vs. 95%, 1 year 63% vs. 90%, 5 years 54% vs. 84%, p = 0.001), while muscle mass was not. In conclusion, muscle mass and quality did not improve after transplant. Muscle quality predicts short- and long-term survival and could help to identify a patient’s risk profile.

Clonal hematopoiesis of indeterminate potential and outcomes after heart transplantation: A multicenter study

Cardiac allograft vasculopathy (CAV) is a leading cause of late graft failure and mortality after heart transplantation (HT). Sharing some features with atherosclerosis, CAV results in diffuse narrowing of the epicardial coronaries and microvasculature, with consequent graft ischemia. Recently, clonal hematopoiesis of indeterminate potential (CHIP) has emerged as a risk factor for cardiovascular disease and mortality. We aimed to investigate the relationship between CHIP and posttransplant outcomes, including CAV. We analyzed 479 HT recipients with stored DNA samples at 2 high-volume transplant centers, Vanderbilt University Medical Center and Columbia University Irving Medical Center. We explored the association between the presence of CHIP mutations with CAV and mortality after HT. In this case-control analysis, carriers of CHIP mutations were not at increased risk of CAV or mortality after HT. In a large multicenter genomics study of the heart transplant population, the presence of CHIP mutations was not associated with an increased risk of CAV or posttransplant mortality.

Decrease of lethal infectious complications in the context of causes of death (COD) after hematopoietic cell transplantation: COD-2 and COD-1 study of the Infectious Diseases Working Party EBMT.

We previously analyzed trends in incidence and factors associated with lethal complications in ALL/AML/CML patients (causes of deaths; COD-1 study). The objective of this study was the analysis of incidence and specific causes of death after HCT, with focus on infectious deaths in two time periods, 1980-2001 (cohort-1) and 2002-2015 (cohort-2). All patients with HCT for lymphoma, plasma cell disorders, chronic leukemia (except CML), myelodysplastic/myeloproliferative disorders, registered in the EBMT-ProMISe-database were included (n = 232,618) (COD-2 study). Results were compared to those in the ALL/AML/CML COD-1 study. Mortality from bacterial, viral, fungal, and parasitic infections decreased in very early, early and intermediate phases. In the late phase, mortality from bacterial infections increased, while mortality from fungal, viral, or unknown infectious etiology did not change. This pattern was similar for allo- and auto-HCT in COD-1 and COD-2 studies, with a distinct and constant lower incidence of all types of infections at all phases, after auto-HCT. In conclusion, infections were the main cause of death before day +100, followed by relapse. Mortality from infectious deaths significantly decreased, except late phase. Post-transplant mortality has significantly decreased in all phases, from all causes after auto-HCT; it has decreased in all phases after allo-HCT except late phase.

New OPTN/UNOS data demonstrates higher than previously reported waitlist mortality for lung transplant candidates supported with ECMO

The use of extracorporeal membrane oxygenation (ECMO) is not currently incorporated into US allocation models due to the historical lack of complete data in the national US registry which changed in 2016 to include ECMO at the time of waitlist removal and more granular timing and configuration data. We studied adult lung transplant candidates from May 1, 2016 to June 1, 2020 with data abstracted from multiple sources in the US Scientific Registry of Transplant Recipients. Waitlist analyses included cumulative incidence functions and Cox proportional hazards models considering ECMO as a time-dependent variable. Post-transplant analyses included Kaplan Meier, Cox proportional hazards models, and observed to expected survival ratios. A total of 867 candidates were on ECMO prior to transplant; 247 were identified using new sources of data. Candidates on ECMO had a 23.9 increased adjusted likelihood of waitlist removal for being too sick or death, but only a 4.08 increased adjusted likelihood of transplant. Candidates bridged with ECMO who underwent lung transplant (N=587) experienced an increased overall hazard of post-transplant mortality with veno-arterial and veno-venous configurations conferring hazard ratio (HR)=1.67 (95% CI, 1.16, 2.40), HR=1.45 (95% CI, 1.15, 1.82), respectively. We identified an additional 28.5% of candidates bridged with ECMO prior to transplant using new data. This study of the newly identified full cohort of ECMO candidates demonstrates higher utilization of ECMO as well as an underestimation of waitlist mortality risk factors that should inform strategies to provide timely access to transplants for this population.

Left ventricular remodeling in end-stage liver disease and post-transplant mortality assessed using end-diastolic pressure-volume relation analysis: Observational retrospective study

Diastolic dysfunction is regarded as an important predictor of outcome after liver transplantation (LT). We investigated the influence of liver disease severity on left ventricular diastolic properties using end-diastolic pressure-volume relationship (EDPVR) analysis in patients with end-stage liver disease (ESLD). Association between alterations of the EDPVR and mortality after LT was evaluated. In this observational retrospective cohort study, 3,211 patients who underwent LT for ESLD were included in analysis. Variables derived from single-beat EDPVR (diastolic stiffness-coefficient [β] and end-diastolic volume at an end-diastolic pressure of 20 mmHg [EDVI20] indicating ventricular capacitance) were estimated using preoperative echocardiographic data. Alterations in EDPVR with increased stiffness (β > 6.16) were categorized into 3 groups; leftward-shifted (EDVI20 <51 mL/m2), rightward-shifted (EDVI20 > 69.7 mL/m2), and intermediate (EDVI20 51-69.7 mL/m2). As the model for ESLD score increases, both EDVI20 and β gradually increased, which indicated ventricular remodeling with larger capacitance and higher diastolic stiffness. Among patients with increased stiffness (β > 6.16, n=1,090), survival rates after LT were lower in leftward-shifted EDPVR than in rightward-shifted EDPVR (73.7% vs 82.9%; log-rank P=0.002). In the adjusted Cox proportional hazard model, risk of cumulative all-cause mortality at 11 years was the highest in leftward-shifted EDPVR (hazard ratio [HR]: 1.93; 95% confidence interval [CI]: 1.27-2.92), followed by intermediate EDPVR (HR: 1.55; 95% CI: 1.12-2.26), compared with rightward-shifted EDPVR. The SHapley Additive exPlanation model revealed that the variables associated with leftward-shifted EDPVR were diabetes, female sex, old age, and hypertension. As ESLD advances, diastolic ventricular properties are characterized by increased EDVI20 and β on rightward-shifted EDPVR, indicating larger capacitance and higher stiffness. However, leftward-shifted EDPVR with left ventricle remodeling failure is associated with poor post-LT survival.

Patient Blood Management in Liver Transplant—A Concise Review

Transfusion of blood products in orthotopic liver transplantation (OLT) significantly increases post-transplant morbidity and mortality and is associated with reduced graft survival. Based on these results, an active effort to prevent and minimize blood transfusion is required. Patient blood management is a revolutionary approach defined as a patient-centered, systematic, evidence-based approach to improve patient outcomes by managing and preserving a patient's own blood while promoting patient safety and empowerment. This approach is based on three pillars of treatment: (1) detecting and correcting anemia and thrombocytopenia, (2) minimizing iatrogenic blood loss, detecting, and correcting coagulopathy, and (3) harnessing and increasing anemia tolerance. This review emphasizes the importance of the three-pillar nine-field matrix of patient blood management to improve patient outcomes in liver transplant recipients.

Abstract 643: Correlations of dietary fiber with intestinal microbiome and outcomes in allogeneic hematopoietic cell transplantation

Abstract Background: Allogeneic hematopoietic cell transplantation (allo-HCT) can be a curative therapy for patients with hematological malignancies. However, allo-HCT poses a significant risk for post-transplant mortality due to graft-versus-host disease (GVHD), which is associated with loss of beneficial intestinal microbiota and decrease of microbial metabolites. In addition, dietary fiber can modulate the intestinal microbiome and the production of short-chain fatty acids (SCFAs), which are microbial metabolites associated with intestinal homeostasis. Therefore, we hypothesized that a high-fiber diet is associated with an increase of beneficial commensals, higher concentrations of SCFAs, and decreased risk of GVHD. Methods: We collected dietary data and fecal samples from 73 allo-HCT patients (GVHD n=45, No-GVHD n=28) at Memorial Sloan Kettering Cancer Center, collected longitudinally throughout the allo-HCT course, and performed 16s rRNA, shotgun metagenomic sequencing, and gas chromatography mass spectrometry (n=311). We assessed the α-diversity, microbiome composition, and concentrations of fecal SCFAs in response to fiber intake. We also tested different concentrations of dietary fiber (0%, 6%, 12% and 40%) in a preclinical GVHD model (C57BL/6J into BALB/c, n=30 per group, n=180 total) and assessed GVHD lethality and fecal microbial composition. Results: We found that in allo-HCT patients, fiber intake significantly correlated with microbial α-diversity (R=0.3, p=0.01) and patients with a higher fiber diet had a significantly higher microbial α-diversity when compared to the low fiber cohort (p&amp;lt;0.001). Remarkably, the decrease in dietary fiber post-allo-HCT correlated with a significant reduction in the fecal concentrations of SCFAs in the GVHD group (n=14), butyrate (p=0.003), propionate (p=0.01), and acetate (p=0.004), that was not significant in the No-GVHD cohort (n=28), indicating that low dietary fiber could lead to lower production of bacterial metabolites in GVHD. In addition, mice receiving a fiber-rich diet (12%) had a significant reduction in GVHD lethality (p=0.02) compared to mice receiving lower or higher fiber (0%, 6%, 40%). A 12% fiber diet also resulted in higher microbial α-diversity (p=0.02) and a significant decrease in Enterococcus faecalis (p=0.05), a pathogen associated with worse GVHD mortality in mice and humans. Conclusions: Our study demonstrates that a) higher fiber intake in patients after allo-HCT is associated with an increase in α-diversity and SCFA concentrations, and b) optimal fiber consumption in pre-clinical GVHD models leads to an increase in α-diversity, a decrease in pathogen mono-domination, and more importantly, a decrease in GVHD lethality. These results suggest that dietary fiber could be used in the prevention of GVHD. Citation Format: Jenny Paredes, Peter Adintori, Anqi Dai, Ruben J. Faustino Ramos, Teng Fei, Harold Elias, Marina Burgos da Silva, Romina Ghale, Charlotte Pohl, Justin Cross, Oriana Miltiadous, Marcel van den Brink. Correlations of dietary fiber with intestinal microbiome and outcomes in allogeneic hematopoietic cell transplantation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 643.

Association between vasoactive-inotropic score, morbidity and mortality after heart transplantation.

The aim of this study was to evaluate the association between vasoactive-inotropic score (VIS), calculated in the 24 h after heart transplantation, and post-transplant mortality and morbidity. This was an observational single-centre retrospective study. Patients admitted to surgical intensive care unit after transplantation, between January 2015 and December 2018, were reviewed consecutively. VISmax was calculated as dopamine+ dobutamine+ 100 × epinephrine + 100 × norepinephrine + 50 × levosimendan + 10 × milrinone (all in µg/kg/min) + 10000 × vasopressin (units/kg/min), using the maximum dosing rates of vasoactive and inotropic medications in the 24 h after intensive care unit admission. The primary outcome was mortality at 1 year post-transplant. The secondary outcomes included length of stay, duration of mechanical ventilation and inotropic support and the occurrence of septic shock, ventilator-associated pneumonia, bloodstream infection or renal replacement therapy. A total of 151 patients underwent heart transplantation and admitted to intensive care unit. The median VISmax was 39.2 (interquartile range = 19.4-83.0). VISmax was independently associated with 1-year post-transplant mortality, as well as recipient age [hazard ratio (HR) = 1.004, P-value = 0.013], recipient gender (female to male: hazard ratio = 2.23, P-value = 0.047) and combined transplantation (hazard ratio = 2.85, P-value = 0.048). There was a significant association between VISmax and duration of mechanical ventilation (P-value < 0.001), length of stay (P-value = 0.002), duration of infused inotropes (P-value < 0.001), occurrence of bloodstream infections, septic shocks, ventilation-acquired pneumonia and renal replacement therapy. VISmax calculated during the first 24 h after postoperative intensive care unit admission in transplanted patients is independently associated with 1-year mortality. In addition, length of stay, duration of mechanical ventilation and infused inotropes increased with increasing VISmax.

(1250) Association Between Acute Rejection Within First Year and Post-Transplant Mortality after Lung Transplantation

(1250) Association Between Acute Rejection Within First Year and Post-Transplant Mortality after Lung Transplantation

(172) Right Ventricular Oversizing Mitigates Post-Transplant Mortality in Recipients with Pulmonary Hypertension

(172) Right Ventricular Oversizing Mitigates Post-Transplant Mortality in Recipients with Pulmonary Hypertension