Sex Differences in Mortality Based on United Network for Organ Sharing Status While Awaiting Heart Transplantation.
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ABSTRACT: There are sex differences in mortality while awaiting heart transplantation, and the reason remains unclear.We included all adults in the Scientific Registry of Transplant Recipients placed on the heart transplant active waitlist from 2004 to 2015. The primary end point was all-cause mortality. Multivariable Cox proportional hazards models were performed to evaluate survival by United Network for Organ Sharing (UNOS) status at the time of listing. Random survival forest was used to identify sex interactions for the competing risk of death and transplantation. There were 33?069 patients (25% women) awaiting heart transplantation. This cohort included 7681 UNOS status 1A (26% women), 13?027 UNOS status 1B (25% women), and 12?361 UNOS status 2 (26% women). During a median follow-up of 4.3 months, 1351 women and 4052 men died. After adjusting for >20 risk factors, female sex was associated with a significant risk of death among UNOS status 1A (adjusted hazard ratio, 1.14; 95% confidence interval, 1.01-1.29) and UNOS status 1B (adjusted hazard ratio, 1.17; 95% confidence interval, 1.05-1.30). In contrast, female sex was significantly protective for time to death among UNOS status 2 (adjusted hazard ratio, 0.85; 95% confidence interval, 0.76-0.95). Sex differences in probability of transplantation were present for every UNOS status, and >20 sex interactions were identified for mortality and transplantation.When stratified by initial UNOS status, women had a higher mortality than men as UNOS status 1 and a lower mortality as UNOS status 2. With >20 sex interactions for mortality and transplantation, further evaluation is warranted to form a more equitable allocation system.
<h4>Background</h4>There are sex differences in mortality while awaiting heart transplantation, and the reason remains unclear.<h4>Methods and results</h4>We included all adults in the Scientific Registry of Transplant Recipients placed on the heart transplant active waitlist from 2004 to 2015. The primary end point was all-cause mortality. Multivariable Cox proportional hazards models were performed to evaluate survival by United Network for Organ Sharing (UNOS) status at the time of listing. R ...[more]
Project description:Young children?<?2 years of age with chronic end-stage liver disease (YC2) are a uniquely vulnerable group listed for liver transplantation, characterized by a predominance of biliary atresia (BA). To investigate wait-list mortality, associated risk factors, and outcomes of YC2, we evaluated United Network for Organ Sharing registry data from April 2003 to March 2013 for YC2 listed for deceased donor transplant (BA?=?994; other chronic liver disease [CLD]?=?221). Overall, wait-list mortality among YC2 was 12.4% and posttransplant mortality was 8%, accounting for an overall postlisting mortality of 19.6%. YC2 demonstrated 12.2%, 18.7%, and 20.6% wait-list mortality by 90, 180, and 270 days, respectively. YC2 with CLD demonstrated significantly higher wait-list mortality compared with BA among YC2 (23.9% versus 9.8%; P?<?0.05). Multivariate analyses revealed that listing Pediatric End-Stage Liver Disease [PELD]?>?21 (hazard ratio [HR], 3.2; 95% confidence interval [CI], 1.6-6.5), lack of exception (HR, 5.8; 95% CI, 2.8-11.8), listing height?<?60.6?cm (HR, 2.1; 95% CI, 1.4-3.1), listing weight ?>?10?kg (HR, 3.8; 95% CI, 1.5-9.2), and initial creatinine?>?0.5 (HR, 6.8; 95% CI, 3.4-13.5) were independent risk factors for YC2 wait-list mortality (P?<?0.005 for all). Adjusting for all variables, the risk of death among CLD patients was 2 (95% CI, 1.3-3.1) times greater than patients with BA?+?surgery (presumed Kasai). Furthermore, the risk of death in BA without surgery was 1.9 (95% CI, 1?3.4) times greater than BA with presumed Kasai. Our data highlight unacceptably high wait-list and early post-liver transplant mortality in YC2 not predicted by PELD and suggest key risk factors deserving of further study in this age group. Liver Transplantation 22 1584-1592 2016 AASLD.
Project description:Light-chain (AL) cardiac amyloidosis (CA) has a worse prognosis than transthyretin (ATTR) CA. In this single-center study, we compared post-heart transplant (OHT, orthotopic heart transplantation) survival for AL and ATTR amyloidosis, hypothesizing that these differences would persist post-OHT. Thirty-nine patients with CA (AL, n = 18; ATTR, n = 21) and 1023 non-amyloidosis subjects undergoing OHT were included. Cox proportional hazards modeling was used to evaluate the impact of amyloid subtype and era (early era: from 2001 to 2007; late era: from 2008 to 2018) on survival post-OHT. Survival for non-amyloid patients was greater than ATTR (P = .034) and AL (P < .001) patients in the early era. One, 3-, and 5-year survival rates were higher for ATTR patients than AL patients in the early era (100% vs 75%, 67% vs 50%, and 67% vs 33%, respectively, for ATTR and AL patients). Survival in the non-amyloid cohort was 87% at 1 year, 81% at 3 years, and 76% at 5 years post-OHT. In the late era, AL and ATTR patients had unadjusted 1-year, 3-year, and 5-year survival rates of 100%, which was comparable to non-amyloid patients (90% vs 84% vs 81%). Overall, these findings demonstrate that in the current era, differences in post-OHT survival for AL compared to ATTR are diminishing; OHT outcomes for selected patients with CA do not differ from non-amyloidosis patients.
Project description:ObjectivesWe hypothesized that an increased duration of donor brain death may worsen survival following orthotopic heart transplantation.MethodsThe United Network for Organ Sharing Registry was queried for first-time, adult recipients of heart transplant from 2006 to 2018. Cox proportional hazards with penalized smooth splines was used to stratify patients based on donor brain death interval: shorter (<22 hours), reference (22-42 hours), and longer (>42 hours). Overall survival was estimated using Kaplan-Meier and Cox proportional hazards models.ResultsA total of 22,960 patients met study criteria (9.2% shorter, 55.0% reference, and 35.8% longer). Longer brain death duration recipients were more likely to have a later year of transplant and have a mechanical bridge to transplant, whereas longer duration donors were more likely to be black and die of anoxia compared with shorter duration and reference donors. Compared with reference, neither shorter (hazard ratio, 1.02; 95% confidence interval, 0.94-1.12) nor longer donor brain death interval (hazard ratio, 1.01; 95% CI, 0.94-1.08) was associated with posttransplant survival in either unadjusted or multivariable analyses (both P values >0.6).ConclusionsLonger duration of brain death was not associated with worse survival following heart transplantation. Donors with prolonged interval of brain death should not necessarily be excluded based on brain death period alone.
Project description:Hepatitis C virus (HCV) infection has been the leading indication for liver transplantation (LT) in the United States. Since 2013, interferon-free antiviral therapy has led to sustained virological response in many LT candidates. We compared the wait-list mortality of HCV patients with that of patients with other chronic liver diseases. Data for primary LT candidates were obtained from the Organ Procurement and Transplantation Network database. Adult wait-list registrants were divided into 3 cohorts: cohort 1 included patients on the waiting list as of January 1, 2004; cohort 2 as of January 1, 2009; and cohort 3 as of January 1, 2014. The primary outcome was wait-list mortality, and the secondary outcome was the rate of change in Model for End-Stage Liver Disease (MELD). Multivariate Cox proportional hazards analysis was performed to evaluate 12-month wait-list mortality. The cohorts included 7627 LT candidates with HCV and 13,748 patients without HCV. Compared with cohort 2, HCV patients in cohort 3 had a 21% lower risk of death (hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.67-0.93). Among patients with non-HCV liver disease, no difference in mortality was seen between cohorts 2 and 3 (HR, 0.97; 95% CI, 0.86-1.09). Among HCV patients, the mean rate of change in MELD decreased from 2.35 per year for cohort 2 to 1.90 per year for cohort 3, compared with 1.90 and 1.66 in cohorts 2 and 3, respectively, among non-HCV patients. In this population-based study, wait-list mortality and progression of disease severity decreased in recent HCV patients for whom direct-acting antiviral agents were available. Liver Transplantation 24 735-743 2018 AASLD.
Project description:ObjectivesThis study examined the impact of the United Network for Organ Sharing (UNOS) policy changes for regional differences in waitlist time and mortality before and after heart transplantation.BackgroundThe 2006 UNOS thoracic organ allocation policy change was implemented to allow for greater regional sharing of organs for heart transplantation.MethodsWe analyzed 36,789 patients who were listed for heart transplantation from January 1999 through April 2012. These patients were separated into 2 eras centered on the July 12, 2006 UNOS policy change. Pre- and post-transplantation characteristics were compared by UNOS regions.ResultsWaitlist mortality decreased nationally (up to 180 days: 13.3% vs. 7.9% after the UNOS policy change, p < 0.001) and within each region. Similarly, 2-year post-transplant mortality decreased nationally (2-year mortality: 17.3% vs. 14.6%; p < 0.001) as well as regionally. Waitlist time for UNOS status 1A and 1B candidates increased nationally 17.8 days on average (p < 0.001) with variability between the regions. The greatest increases were in Region 9 (59.2-day increase, p < 0.001) and Region 4 (41.2-day increase, p < 0.001). Although the use of mechanical circulatory support increased nearly 2.3-fold nationally in Era 2, significant differences were present on a regional basis. In Regions 6, 7, and 10, nearly 40% of those transplanted required left ventricular assist device bridging, whereas only 19.6%, 22.3%, and 15.5% required a left ventricular assist device in regions 3, 4, and 5, respectively.ConclusionsThe 2006 UNOS policy change has resulted in significant regional heterogeneity with respect to waitlist time and reliance on mechanical circulatory support as a bridge to transplantation, although overall both waitlist mortality and post-transplant survival are improved.
Project description:Patients with end-stage renal disease (ESRD) have impaired functional status compared with the general population. We sought to explore the association between Karnofsky Performance Status (KPS) and death/delisting from the kidney transplantation waitlist and whether this association differed by age. Patients listed for single-organ kidney transplantation in the United Network for Organ Sharing/Organ Procurement and Transplantation Network from January 1, 2015, to January 1, 2018, were included. We performed competing-risk regression analyses to determine the association between KPS ("Severely impaired", "Moderately impaired", "Non-impaired") and death/delisting, with deceased-donor kidney transplantation as a competing risk. We tested for interactions between age and KPS on death/delisting. Of the 89,819 patients analyzed, 39% were impaired (KPS < 80) and 20% were aged ≥ 65 years. Older age and lower KPS were independently associated with higher risk of death/delisting (age 45-64 years, HR 1.97 [95% CI 1.73-2.24]; age ≥ 65 years, HR 3.62 [95% CI 3.33-3.92] compared with age < 45 years; moderately impaired, HR 1.68 [95% CI 1.45-1.95]; severely impaired, HR 4.80 [95% CI 3.71-6.21] compared with non-impaired). Lower KPS was associated with higher risk of death/delisting among all ages, but this effect was slightly less pronounced among individuals aged ≥ 65 years. Performance status should be used when counseling patients with ESRD on their risks for death/delisting.
Project description:BackgroundSurvival of patients on left ventricular assist devices (LVADs) has improved. We examined the differences in risk of adverse outcomes between LVAD-supported and medically managed candidates on the heart transplant waiting list.Methods and resultsWe analyzed mortality and morbidity in 33,073 heart transplant candidates registered on the United Network for Organ Sharing (UNOS) waiting list between 1999 and 2011. Five groups were selected: patients without LVADs in urgency status 1A, 1B, and 2; patients with pulsatile-flow LVADs; and patients with continuous-flow LVADs. Outcomes in patients requiring biventricular assist devices, total artificial heart, and temporary VADs were also analyzed. Two eras were defined on the basis of the approval date of the first continuous-flow LVAD for bridge to transplantation in the United States (2008). Mortality was lower in the current compared with the first era (2.1%/mo versus 2.9%/mo; P<0.0001). In the first era, mortality of pulsatile-flow LVAD patients was higher than in status 2 (hazard ratio [HR], 2.15; P<0.0001) and similar to that in status 1B patients (HR, 1.04; P=0.61). In the current era, patients with continuous-flow LVADs had mortality similar to that of status 2 (HR, 0.80; P=0.12) and lower mortality compared with status 1A and 1B patients (HR, 0.24 and 0.47; P<0.0001 for both comparisons). However, status upgrade for LVAD-related complications occurred frequently (28%) and increased the mortality risk (HR, 1.75; P=0.001). Mortality was highest in patients with biventricular assist devices (HR, 5.00; P<0.0001) and temporary VADs (HR, 7.72; P<0.0001).ConclusionsMortality and morbidity on the heart transplant waiting list have decreased. Candidates supported with contemporary continuous-flow LVADs have favorable waiting list outcomes; however, they worsen significantly once a serious LVAD-related complication occurs. Transplant candidates requiring temporary and biventricular support have the highest risk of adverse outcomes. These results may help to guide optimal allocation of donor hearts.
Project description:BackgroundReduced BMI is an absolute contraindication for lung transplantation (LTx) at most centers in the United States. The objective of this study was to quantify post-LTx survival of moderate to severely underweight patients with cystic fibrosis (CF) (BMI < 17 kg/m2) in the United States relative to normal-weight recipients with CF and other frequently transplanted patient cohorts.MethodsUsing United Network for Organ Sharing Registry data (undergoing transplant from June 2005-November 2015), Kaplan-Meier estimates of median posttransplant survival were calculated for all patients with CF, COPD, and idiopathic pulmonary fibrosis (IPF), as well as low and normal weight CF subgroups. Cox regression modeling stratified according to transplant center assessed risk of posttransplant mortality in recipients with CF and a BMI < 17 kg/m2 compared with recipients with COPD (reference).ResultsMedian posttransplant survival (95% CI) for CF, COPD, and IPF was 7.9 (7.2-8.6), 5.9 (5.6-6.2), and 5.5 (5.2-5.8) years, respectively. Although an absolute decrease was noted in posttransplant survival for recipients with CF and a BMI < 17 kg/m2, compared with those with CF and a BMI ≥ 17 kg/m2 (7.0 years [4.5-7.9] vs 8.2 years [7.3-9.0]), Cox modeling found no increased mortality risk (adjusted hazard ratio, 1.09; 95% CI, 0.90-1.32; P = .38). There was no difference in posttransplant mortality between patients with CF and a BMI < 17 kg/m2 and recipients with COPD and all BMIs (adjusted hazard ratio, 1.04; 95% CI, 0.86-1.25; P = .71).ConclusionsTransplant recipients with CF and a BMI < 17 kg/m2 had posttransplant survival rates comparable to those of other groups frequently undergoing transplantation. BMI < 17 kg/m2 as a single risk factor in the CF population should not be treated as an absolute contraindication to LTx.
Project description:AimsWhether sex affects selection for and outcomes after heart transplantation (HTx) remains unclear. We aimed to show sex differences in pre-transplant characteristics and outcomes after HTx.Methods and resultsFrom 1995 to 2019, 49 200 HTx recipients were prospectively enrolled in the Organ Procurement and Transplantation Network. Logistic regression models were used to evaluate clinical characteristics by sex. Multivariable Cox regression models were fitted to assess sex differences in all-cause mortality, cardiovascular mortality, graft failure, cardiac allograft vasculopathy (CAV), and malignancy. In 49 200 patients (median age 55 years, interquartile range 46-62; 24.6% women), 49 732 events occurred during a median follow-up of 8.1 years. Men were older than women, had more often ischaemic cardiomyopathy (odds ratio [OR] 3.26, 95% confidence interval [CI] 3.11-3.42; P < 0.001), and a higher burden of cardiovascular risk factors, whereas women had less malignancies (OR 0.47, CI 0.44-0.51; P < 0.001). Men were more often treated in intensive care unit (OR 1.24, CI 1.12-1.37; P < 0.001) with a higher need for ventilatory (OR 1.24, CI 1.17-1.32; P < 0.001) or VAD (OR 1.53, CI 1.45-1.63; P < 0.001) support. After multivariable adjustment, men had a higher risk for CAV (hazard ratio [HR] 1.21, CI 1.13-1.29; P < 0.001) and malignancy (HR 1.80, CI 1.62-2.00; P < 0.001). There were no differences in all-cause mortality, cardiovascular mortality, and graft failure between sexes.ConclusionsIn this US transplant registry, men and women differed in pre-transplant characteristics. Male sex was independently associated with incident CAV and malignancy even after multivariable adjustment. Our results underline the need for better personalized post-HTx management and care.
Project description:BackgroundThe hemodynamic effects of pre-transplant vaccination against COVID-19 among heart transplant candidates hospitalized for advanced heart failure remains unknown.MethodsA retrospective chart review was conducted at a high-volume transplant center from January through December 2021. 22 COVID-19 vaccination events occurred among patients hospitalized for decompensated heart failure while awaiting transplantation. Primary outcomes included inotrope and vasopressor dosages. Secondary outcomes included vital signs, pulmonary artery catheter measurements, diuretic dosages, and renal function. Data were extracted 24 h before through 72 h after vaccination.ResultsOne of 22 vaccination events was associated with hemodynamic changes requiring increased inotropic and vasopressor support post-vaccination. In all other cases, transient hemodynamic changes occurred without need for escalated therapy.ConclusionsCOVID-19 vaccination can be administered safely to most critically ill patients with advanced heart failure including those awaiting transplantation. All patients should be monitored closely as some may be susceptible to significant hemodynamic changes.