Heart Transplant Waitlist Research Articles

Association of center-level temporary mechanical circulatory support use and waitlist outcomes after the 2018 adult heart allocation policy

BackgroundThe present study characterizes the association of center-level temporary mechanical circulatory support use with waitlist outcomes after the 2018 adult heart allocation policy change. MethodsThe United Network for Organ Sharing database was queried for all single-organ, adult heart transplant candidates from November 2015 to October 2021. The study population was divided into 2 cohorts, prepolicy and postpolicy, centered around the rule change on October 18, 2018. The primary study outcome was center-level rate of poor waitlist outcome, defined as death or deterioration on the waitlist. Competing-risks regression was used to generate risk-adjusted rates of poor waitlist outcome at each center, while Pearson’s correlation coefficient (r) was used to assess the significance of center-level temporary mechanical circulatory support use (defined as the proportion listed with temporary mechanical circulatory support) and poor waitlist outcome. ResultsOf 22,077 transplant candidates included in analysis, 50.5% were listed during postpolicy. Compared to prepolicy, postpolicy candidates were more often listed with temporary mechanical circulatory support and less commonly listed with a durable left-ventricular assist device. The proportion of hospitals not using any temporary mechanical circulatory support decreased significantly from prepolicy to postpolicy (15% to 1%, P < .001). During prepolicy, center-level temporary mechanical circulatory support use showed no correlation with adjusted poor waitlist outcome. However, center-level temporary mechanical circulatory support use showed a negative correlation with poor waitlist outcome during postpolicy (r = -0.42, P < .001). ConclusionThe 2018 adult heart allocation policy appears to benefit patients listed at high temporary mechanical circulatory support using centers, with significant interhospital variation in temporary mechanical circulatory support use in the new era. Given the growing role of temporary mechanical circulatory support on the heart transplant waitlist, greater standardization of its application is warranted.

Challenges in Heart Transplantation During COVID-19 Pandemic in Brazil

PurposeA recent UNOS analysis comparing COVID-19 to pre-COVID-19 era found an increased waitlist inactivation, decreased waitlist addition, and decreased in numbers of heart transplant (HT). In Brazil, a pronounced negative effect on transplant was anticipated but has not been measured so far. Our objective was to evaluate the impact of COVID-19 pandemic on heart donation and HT.MethodsWe performed a descriptive analysis of data related to patients registered in HT waitlist and numbers of HT performed from March 2018 to August 2019 (pre-COVID era) and March 2020 to August 2021 (COVID era), by reviewing medical records and data from State Transplant System.ResultsA total of 221 patients were included in HT waitlist from 2018 to 2021. Approximately the same number of patients were listed in pre-COVID and COVID era (111 vs 110, respectively). Mean age of patients were 48.7 in the pre COVID and 48.9 years in the COVID era (p=0.91). The majority were listed as top priority criteria, 94 (85.5%) in COVID vs 100 (90.1%) in pre-COVID era, p=0.293, mostly due to mechanical circulatory assist devices ECMO and Centrimag (10.9% vs 18%), and intra-aortic balloon pump (41.8 % vs 39.6%) respectively, p=0.496. There was no difference in the survival of patients in waitlist (p = 0.226). Regarding number of HT, we observed highest absolute number of surgeries in the pre-COVID era (78 vs 66), with no statistical significance (p=0.109). There was no difference between the deaths after HT, 17 (15.3%) in pre-COVID and 9 (8.2%) in COVID era, p=0.249. During the peak of number of COVID-19 cases in Brazil (may-july 2020 and february-april 2021) we observe a reduction in overall heart transplant procedures an inclusion in waitlist (figure).ConclusionTo the best of our knowledge, this is the first report of the impact of COVID - 19 on solid organ donation and HT. There were no differences between number of patients included in HT waitlist and outcomes after HT before and during COVID. However, there was a decrease in number of HT and inclusion in HT waitlist during the peak of COVID-19.

Sex Disparities in Heart Transplant Waitlist Status After the Donor Heart Allocation Policy Change

<h3>Purpose</h3> There are many reports in solid organ transplantation that demonstrate that there are sex discrepancies in waitlist urgent status, time on the transplant waitlist, and waitlist mortality. There should be no differences in men versus women in the percent of patients with severe heart disease. The new donor heart allocation policy change took place in October 2018, and provided the sickest patients with the highest priority for donor hearts. We chose to assess our male and female patients to establish whether there exists a difference in patients listed as urgent status on the heart transplant (HTx) waitlist. <h3>Methods</h3> Between November 2018 and December 2020 (after donor heart allocation change in October 2018), we assessed 276 patients on our HTx waitlist. Patients on the HTx waitlist were followed for 6 months and censored after they were transplanted or removed from the waitlist. Percent of patients of each sex listed as urgent status (status 1, 2, 3) was recorded. Mortality on the waitlist, waitlist time, and removal from the waitlist due to being too sick were secondary endpoints. <h3>Results</h3> After the donor heart allocation policy change in October 2018, women were significantly less likely to be listed as urgent status compared to men. For those patients listed as urgent status, there was no significant difference in mortality for women versus men on the HTx waitlist. Average waitlist time was similar between the 2 groups. (see table) <h3>Conclusion</h3> There appears to be a sex disparity for women being less likely to be listed as urgent status on the HTx waitlist. Further studies are needed to determine whether this difference has a biologic mechanism or whether there is selection bias and/or treatment bias present in their care.

The Impact of Utilizing DCD Donor Hearts on Heart Transplant Activity and Waitlist Time

<h3>Purpose</h3> Machine perfusion of donated organs after declaration of circulatory death (DCD) allows for the use of hearts previously discarded as not usable for transplantation. This opportunity potentially expands the donor pool and decreases waitlist time. This study aims to examine the impact of utilizing DCD hearts on heart transplant waitlist time <h3>Methods</h3> We retrospectively analyzed 161 patients who were listed for heart transplant from September 2019 through September 2021 at our center. These patients were separated into 2 periods centered on September 12, 2020 when transplantation of DCD donor hearts began <h3>Results</h3> Baseline patient characteristics were similar between both periods. In Period 1, 76 patients were waitlisted with 70 transplants occurring during this period, whereas in Period 2, 85 patients were waitlisted with 88 transplants occurring in this period. Thirty DCD donor heart transplants were performed in Period 2 (34% of period 2 transplants).Year over year transplant activity increased by 25.7%. Transplant rate increased from 2.06 person-year in Period 1 to 3.1 person-year in Period 2.There was no significant difference between the two periods with respect to waitlist mortality rate, length of post-transplant hospital stay, and short-term post-transplant survival. Median waiting time from listing to transplant was 17 days in Period 1 and 27 days in Period 2.There was no difference in blood types and United Network for Organ Sharing (UNOS) listing status between Period 1 and Period 2. <h3>Conclusion</h3> Our single-center analysis demonstrates that utilization of DCD donor hearts has resulted in an increase in transplant rate. Further extended follow-up is needed to determine long-term safety and efficacy of this strategy.

Efficacy of Tocilizumab for Refractory Sensitized Patients Awaiting Heart Transplantation

<h3>Purpose</h3> Sensitization in patients (pts) awaiting heart transplantation (HTx) can be refractory to conventional therapies such as plasmapheresis, intravenous immunoglobulin (IVIG), rituximab, and bortezomib, particularly for Class II antibodies. Pts refractory to these initial therapies may require more advanced therapies. Tocilizumab is an anti-interleukin-6 monoclonal antibody found to significantly reduce dominant HLA antibodies prior to kidney transplantation. We report here our experience with tocilizumab in refractory sensitized pts awaiting HTx. <h3>Methods</h3> Between 2008 and 2020, we assessed 7 HTx pts who were initially treated with conventional desensitization therapies, including plasmapheresis, IVIG, rituximab, and bortezomib. Pts were then treated with tocilizumab at 8 mg/kg monthly for 6 months. Endpoints included change in calculated panel reactive antibodies (CPRA) determined just prior to the administration of tocilizumab, and 2 weeks after completion of the 6-month therapy. Antibodies were further classified into Class I and Class II to assess efficacy in each of these subgroups. 1 year post-HTx antibody mediated rejection (AMR) and survival was assessed and compared with pts transplanted without desensitization therapy in the same period (N=302). <h3>Results</h3> 6 of 7 sensitized pts treated with tocilizumab had a decrease in their immunodominant antibody with an average 31% reduction. For the CPRA level, 4 of 7 patients had a predominant decrease in Class II circulating antibodies. Post-HTx, compared to pts who did not receive desensitization therapies, 1st year AMR episodes were increased in the tocilizumab group (2.0% vs 14.3% respectively; p=0.032) but this did not affect survival at 1 year (92.1% vs 100% respectively; p=0.447). <h3>Conclusion</h3> Highly sensitized pts on the heart transplant waitlist who are refractory to conventional desensitization therapy appear to be responsive to tocilizumab therapy. Although these pts have more AMR post-transplant, survival is comparable.

Status Exceptions and Racial Disparities in Pediatric Heart Transplant Waitlist Outcomes

<h3>Purpose</h3> The 2016 revision of the US Pediatric Heart Allocation Policy (USPHAP) created more stringent rules for priority status. We evaluated the hypothesis that resultant differential status exceptions based on race contribute to racial disparities in waitlist outcomes. <h3>Methods</h3> The Scientific Registry for Transplant Recipients database was queried for children listed for first heart-alone transplant from January 2012 to June 2020. Waitlist status & mortality with regards to race were evaluated, stratified by listing before (Era 1) or after (Era 2) the policy change. <h3>Results</h3> The use of both status 1A and 1B exceptions (E) increased in Era 2 (1A(E): 5% in Era 1 vs 12%, p<0.001; 1B(E): 6% vs 10%, p <0.001). In Era 1, there was no association between patient race/ethnicity and use of 1A(E) or 1B(E) when controlling for age and diagnosis. In Era 2, race/ethnicity was not associated with 1A(E) but was associated with 1B(E): non-Hispanic (NH) Black children were significantly less likely to be listed 1B(E) compared to NH White children (OR 0.46 [95% CI 0.31-0.68]) or Hispanic children (OR 0.52 [95% CI 0.33-0.84)) with similar ages and diagnoses. Among children initially listed status 1B or 2 in Era 2, those with status 1B(E) had lower waitlist mortality when controlling for age, diagnosis, and renal function (aHR 0.3 [95% CI 0.1-0.8]). In Era 1, there were no significant differences in waitlist mortality based on race/ethnicity at any waitlist status; in Era 2, however, NH Black children had higher waitlist mortality than NH White children when initially listed 1B or 2 (Figure 1). <h3>Conclusion</h3> Since the 2016 USPHAP change, racial disparities in waitlist mortality have worsened among children initially listed with lower priority status. While 1B(E) status is associated with lower mortality risk, a lack of exceptions being sought for Black children contributes to their higher mortality. Standardized exception guidance and pediatric specific review boards (both implemented after this study period) have the potential to improve equity.

Right and left ventricular assist devices are an option for bridge to heart transplant

BackgroundPatients with a left ventricular assist device with right ventricular failure are prioritized on the heart transplant waitlist; however, their post-transplant survival is less well characterized. We aimed to determine whether pretransplant right ventricular failure affects postoperative survival in patients with a left ventricular assist device as a bridge to transplant. MethodsWe performed a retrospective review of the 2005-2018 Organ Procurement and Transplantation Network/United Network for Organ Sharing registry for candidates aged 18 years or more waitlisted for first-time isolated heart transplantation after left ventricular assist device implantation. Candidates were stratified on the basis of having right ventricular failure, defined as the need for right ventricular assist device or intravenous inotropes. Baseline demographic and clinical characteristics were compared among the 3 groups, and post-transplant survival was assessed. ResultsOur cohort included 5605 candidates who met inclusion criteria, including 450 patients with right ventricular failure, 344 patients with a left ventricular assist device and intravenous inotropes as a bridge to transplant, 106 patients with a left ventricular assist device and right ventricular assist device, and 5155 patients with a left ventricular assist device as a bridge to transplant without the need for right side support. Compared with patients without right ventricular failure, patients with a left ventricular assist device as a bridge to transplant with right ventricular failure were younger (median age 51 years, 55 vs 56 years, P < .001) and waited less time for organs (median 51 days, 93.5 vs 125 days, P < .001). These patients also had longer post-transplant length of stay (median 18 days, 20 vs 16 days, P < .001). Right ventricular failure was not associated with decreased post-transplant long-term survival on unadjusted Kaplan–Meier analysis (P = .18). Neither preoperative right ventricular assist device nor intravenous inotropes independently predicted worse survival on multivariate Cox proportional hazards analysis. However, pretransplant liver dysfunction (total bilirubin >2) was an independent predictor of worse survival (hazard ratio, 1.74; 95% confidence interval, 1.39-2.17; P < .001), specifically in the left ventricular assist device group and not in the left ventricular assist device + right ventricular assist device/intravenous inotropes group. ConclusionsPatients with biventricular failure are prioritized on the waiting list, because their critical pretransplant condition has limited impact on their post-transplant survival (short-term effect only); thus, surgeons should be confident to perform transplantation in these severely ill patients. Because liver dysfunction (a surrogate marker of right ventricular failure) was found to affect long-term survival in patients with a left ventricular assist device, surgeons should be encouraged to perform transplantation in these severely ill patients after a recipient's optimization by inotropes or a right ventricular assist device because even when the bilirubin level is elevated in these patients (treated with right ventricular assist device/inotropes), their long-term survival is not affected. Future studies should assess recipients' optimization before organ acceptance to improve long-term survival.

Abstract 8999: Impact of Coronavirus 2019 on Pediatric and Adult Heart Transplantation Waitlist Activity and Mortality in the United States

Introduction: Transplant centers saw a reduction in solid organ transplantation since the beginning of the coronavirus 2019 (COVID-19) pandemic in the United States. Limited data exists on the impact of COVID-19 on pediatric heart transplant volume and variation in transplant practices. We hypothesized that pediatric heart transplant activity decreased during COVID-19 with associated increased waitlist mortality. Methods: The United Network for Organ Sharing (UNOS) database was used to identify waitlisted patients from 2017-2020. Regional and Statewide data was obtained from US Census Bureau. CovidActNow project was used for Covid-19 mortality rates. Results: Among pediatric patients, average time on the waiting list decreased by 28 days. Even though the average number of pediatric transplants (n=39) did not change during 2020, there was a temporal decline in the first quarter followed by an increase. Overall pediatric waitlist mortality decreased from 5.31 to 4.73, however female mortality increased by 2%. Regional differences in pediatric mortality included: Northeast, decreased by 7.5%; Midwest, decreased by 9%; West, increased by 3.5%; and South, increased by 13%. North Dakota (0.55), Oklahoma (0.21) and Hawaii (0.33) showed higher mortality per 100,000 than other states. In adults, average time on waiting list increased by 40 days and there was an increase in the number of transplants from 242.06 to 266.09. Adult waitlist mortality had a larger decrease from 18.44 to 15.70 with increase in female mortality of 7%. Regional differences in adult mortality included: Northeast, decreased by 3%; Midwest, increased by 5.5%; West, increased by 4.5% and South, decreased by 5%. Iowa (0.37), Wyoming (0.22), Arkansas (0.18) and Vermont (0.19) had higher mortality per 100,000 than other states . Conclusions: Pediatric heart transplant volume declined in early 2020 followed by an increase, while transplant volume in adults increased. Although, overall waitlist mortality for pediatrics decreased, female waitlist mortality increased. Regional differences in waitlist mortality were also observed. Future studies are needed to understand this initial correlation and to determine the impact of COVID-9 on heart transplant recipients.

Sex disparities in the current era of pediatric heart transplantation in the United States

While sex-related differences in transplant outcomes have been well characterized amongst adults, there are no sex-specific pediatric heart transplant studies over the last decade and none evaluating waitlist outcomes. In a contemporary cohort of children undergoing heart transplantation in the United States, this analysis was performed to determine if there were sex disparities in waitlist and/or post-transplant outcomes. Retrospective review of Scientific Registry of Transplant Recipients database from December 16, 2011 to February 28, 2019 to compare male and female children after listing and after transplant. Demographic, clinical characteristics and outcomes were compared unadjusted and after 1:1 propensity matching for selected covariates. Of 4089 patients, 2299 (56%) were males. At listing, males were more likely to be older, have congenital heart disease (58% vs 48%), renal dysfunction (49% vs 44%) and implantable cardioverter defibrillator (9% vs 7%). At transplant, males were more likely to have renal (42 % vs 35%) and liver dysfunction (13% vs 10%), PRA >10% (29% vs 22%) and ischemic time >3.5 hours (p < 0.05 for all). There were no significant sex differences found in unadjusted rates of transplant or mortality. After propensity matching, females had increased waitlist mortality (HR 1.3, 95%CI 1.04-1.5; p =0.019) compared to males. There were no significant differences in post-transplant morbidity or mortality (HR 1.2, 95% CI 0.93-1.5; p=0.18) between groups. In a contemporary pediatric cohort, females have inferior heart transplant waitlist survival compared to propensity-matched males despite lower acuity of illness at listing and similar rates of transplantation. There were no sex-disparities noted in post-transplant outcomes.

Posttransplant Long-Term Outcomes for Patients with Ventricular Assist Devices on the Heart Transplant Waitlist.

Ventricular assist devices (LVADs) are commonly used in end-stage heart failure for mechanical circulatory support as a bridge to heart transplantation. However, LVADs' long-term effects on posttransplant survival are unknown. We sought to compare long-term mortality after transplantation for patients with and without LVADs. Using the Organ Procurement and Transplantation Network database, we investigated LVADs' impact on long-term (3 month, 1 year, 2 years, 5 years, and 8 years) posttransplant mortality risk for all heart transplant recipients between 2010 and 2019. Time-to-event regression analysis quantified mortality risk by LVAD status in both unconditional and conditional survival analyses. Of 20,113 transplant recipients, 8,999 (45%) had a LVAD while on the waitlist. Among those who died after transplantation, patients with LVADs on average died sooner (1.8 years) than patients without LVADs (3.0 years; p < 0.01). On multivariable analysis, patients with LVADs had a 44% higher mortality risk within the first 3 months posttransplant (HR = 1.44, p = 0.03). There was no significant difference in mortality risk between patients who did and did not have pretransplant LVADs after 1, 2, and 5 years of posttransplant conditional survival. While LVAD patients have a survival disadvantage in the first year posttransplant, conditional survival analysis demonstrated no difference in mortality risk between patients with and without LVADs beyond 1 year of follow up. Of the patients who died posttransplant, patients with LVADs on average died sooner than patients without LVADs.

Changing Demographics, Temporal Trends in Waitlist, and Posttransplant Outcomes After Heart Transplantation in the United States: Analysis of the UNOS Database 1991-2019.

We sought to investigate temporal trends in patient characteristics, waitlist, and posttransplant outcomes after heart transplantation in the United States. Using data from the United Network of Organ Sharing, we identified adults listed for heart transplantation between 1991 and 2019. Patients were divided into 4 eras based on the 3 time points in which changes were made to the patient selection/allocation policy (Era 1=January 1991-January 1999; Era 2=January 1999-July 2006; Era 3=July 2006-October 2018; and Era 4=October 2018-March 2020), and patient characteristics, waitlist, and posttransplant outcomes were evaluated for each era. Between 1991 and 2019, 95 179 patients were added to the heart transplantation waitlist. Compared with Era 1, patients listed in Era 4 were older (mean age: 50 versus 52 years) and with higher risk comorbidities (eg, 10% versus 28.8% diabetes, 23.3% versus 35.6% obese). Over the study period, 22 738 patients died or were permanently delisted for deterioration on the waitlist while 61 687 were transplanted. Compared with the preceding era, there was significant decrease in death or deterioration in the last 2 eras (sub-hazard ratio, 0.67 [95% CI, 0.65-0.70] for Era 3 versus Era 2 and sub-hazard ratio, 0.65 [95% CI, 0.58-0.73] for Era 4 versus 3). Across the years, 27.1% to 40.5% of those on the waitlist were transplanted. Among those 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%-17.1%), and length-of-stay (14-17days), P<0.001. However, this did not negatively impact short-term survival when compared with the preceding era (1-year graft survival from Era 1 to Era 4=84.1%, 86.4%, 90.4%, and 89.7%, respectively). There have been significant changes in the characteristics of patients listed for heart transplantation. Although transplant volume has increased, the wide supply-demand gap persisted. The last two changes in the allocation policy achieved their primary objective of reducing waitlist mortality.

Impact of Coronavirus-2019 On Pediatric and Adult Heart Transplantation Waitlist Activity and Mortality in The United States: A Descriptive Approach

BackgroundTransplant centers saw a substantial reduction in deceased donor solid organ transplantation since the beginning of the coronavirus 2019 (COVID-19) pandemic in the United States. There is limited data on the impact of COVID-19 on adult and pediatric heart transplant volume and variation in transplant practices. We hypothesized that heart transplant activity decreased during COVID-19 with associated increased waitlist mortality. MethodsThe United Network for Organ Sharing (UNOS) database was used to identify patients at the time of listing for heart transplant from 2017–2020. Patients were categorized as pediatric (<18 years) or adult (≥18 years) and as pre-COVID (2017-2019) or post-COVID (2020). Regional and statewide data were taken from United States Census Bureau. CovidActNow project was used to obtain COVID-19 mortality rates. FindingsAmong pediatric patients, average time on the waiting list decreased by 28 days. Even though the average number of pediatric transplants (n=39 per month) did not change significantly during 2020, there was a temporal decline in the first quarter of 2020 followed by a sharp increase. Overall absolute pediatric waitlist mortality decreased from 5•31 to 4•73, however female mortality increased by 2%. Regional differences in pediatric mortality were observed: Northeast, decreased by 7•5%; Midwest, decreased by 9%; West, increased by 3•5%; and South, increased by 13%. North Dakota (0•55), Oklahoma (0•21) and Hawaii (0•33) showed higher mortality than other states per 100,000. In adults, average time on waiting list increased by 40 days and there was an increase in the number of transplants from 242 to 266. Adult waitlist mortality had a larger decrease, 18•44 to 15•70, with an increase in female mortality of 7%. Regional differences in adult mortality were also observed: Northeast, decreased by 3%; Midwest, increased by 5•5%; West, increased by 4•5% and South, decreased by 5%. Iowa (0•37), Wyoming (0•22), Arkansas (0•18) and Vermont (0•19) had the highest mortality per 100,000 compared to the other states. InterpretationPediatric heart transplant volume declined in early 2020 followed by a later increase, while adult transplant volume increased all year round. Although, overall pediatric waitlist mortality decreased, female waitlist mortality increased for both adults and pediatrics. Regional differences in waitlist mortality were observed for both pediatrics and adults. Future studies are needed to understand this initial correlation and to determine the impact of COVID-19 on heart transplant recipients FundingThis research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

The Genetically Engineered Heart as a Bridge to Allotransplantation in Infants Just Around the Corner?

BackgroundMortality for infants on the heart transplant waitlist remains unacceptably high, and available mechanical circulatory support is suboptimal. Our goal is to demonstrate the feasibility of utilizing genetically engineered pig (GEP) heart as a bridge to allotransplantation by transplantation of a GEP heart in a baboon. MethodsFour baboons underwent orthotopic cardiac transplantation from GEP donors. All donor pigs had galactosyl-1,3-galactose knocked out. Two donor pigs had human complement regulatory CD55 transgene and the other 2 had human complement regulatory CD46 and thrombomodulin. Induction immunosuppression included thymoglobulin, and anti-CD20. Maintenance immunosuppression was rapamycin, anti-CD-40, and methylprednisolone. One donor heart was preserved with University of Wisconsin solution and the other three with del Nido solution. ResultsAll baboons weaned from cardiopulmonary bypass. B217 received a donor heart preserved with University of Wisconsin solution. Ventricular arrhythmias and depressed cardiac function resulted in early death. All recipients of del Nido preserved hearts easily weaned from cardiopulmonary bypass with minimal inotropic support. B15416 and B1917 survived for 90 days and 241 days, respectively. Histopathology in B15416 revealed no significant myocardial rejection but cellular infiltrate around Purkinje fibers. Histopathology in B1917 was consistent with severe rejection. B37367 had uneventful transplant but developed significant respiratory distress with cardiac arrest. ConclusionsSurvival of B15416 and B1917 demonstrates the feasibility of pursuing additional research to document the ability to bridge an infant to cardiac allotransplant with a GEP heart.

Impact of changing renal function, while waiting for a heart transplant, on post-transplant mortality and development of end stage kidney disease.

Heart transplantation is a viable option for end stage heart disease but long-term complications such as chronic kidney disease are being increasingly recognized. We sought to investigate the effect of change in estimated glomerular filtration rate (eGFR) during the heart transplant waitlist period on post-transplant mortality and end stage kidney disease (ESKD). We analysed the United Network of Organ Sharing heart transplant database from 2000 to 2017. Multivariable Cox regression with restricted cubic splines and cumulative incidence competing risk (CICR) methods were used to compare the effects of change in eGFR on mortality and ESKD, respectively. A total of 19412 patients met our inclusion criteria. Mortality increased with increasing loss of eGFR (adjusted hazard ratio increased from 1.02 [confidence interval (CI) 1.01-1.04, P=0.008] for 10% loss to 1.15 (CI 1.06-1.26, P=0.001) for 50% loss of eGFR. Similarly, risk of ESKD also increased monotonically with increasing loss of renal function [subdistribution hazard ratio increased from 1.12 (CI 1.09-1.14, P<0.001) to 2.0 (CI 1.74-2.3, P<0.001)] as loss of eGFR increased from 10% to 50%. Overall, we found that loss of >10% of eGFR resulted in higher risk of mortality and higher risk of ESKD.

Waitlist Mortality for Children Listed for Heart Transplant in the United States: How are We Doing?

PurposeStudies suggest that pediatric heart transplant (HT) waitlist mortality has declined. The impact of factors like refinements to the heart allocation system, patient selection, greater ABO incompatible (ABO-I) HT and VAD support are unknown. We examined the 20-year trend in waitlist mortality to identify factors associated with declining mortality and whether allocational inefficiencies persist.MethodsAll children <18 years listed for isolated HT from 1999-2020 were identified using OPTN data and grouped into 3 eras (Era 1: 1999-2006; Era 2: 2006-2016; Era 3: 2016-2020) based on when UNOS revised the heart allocation system. Cox proportional hazards modeling was used to identify factors associated with death or delisting due to deterioration.ResultsOverall 11,374 patients met inclusion criteria (3,248 in Era 1; 5,378 in Era 2; 2,748 in Era 3). Waitlist mortality declined significantly across eras (21%, 17%, 13%, P<0.001). The prevalence at listing of major risk factors for mortality declined across eras including a reduction by 47% in ECMO use (11% to 6%, P<0.001), 33% in ventilator use (27% to 18%, P<0.001), 26% in dialysis use (2.5% to 1.8%, P=0.08); in contrast VAD use at listing increased by 243% (6% to 15%, P<0.001). Infant mortality declined significantly (27% to 20%, P<0.001) with a 48% decline in mortality for blood group O patients (relative to the background decline for all blood groups) and a 69% decline in infant VAD mortality (P<0.01). In Era 3, RCM and re-transplant patients not eligible for status 1A without exception had higher mortality than 1A DCM patients on LVAD support (16% vs 5.3%, P<0.01).ConclusionPediatric HT waitlist mortality has declined significantly over the past 20 years. There is evidence to suggest that greater VAD use, revisions to organ allocation, refinements in patient selection and ABO-I transplant may all contribute. Organ allocation inefficiencies persist under the current allocation system suggesting opportunities for allocation improvement may still exist. Studies suggest that pediatric heart transplant (HT) waitlist mortality has declined. The impact of factors like refinements to the heart allocation system, patient selection, greater ABO incompatible (ABO-I) HT and VAD support are unknown. We examined the 20-year trend in waitlist mortality to identify factors associated with declining mortality and whether allocational inefficiencies persist. All children <18 years listed for isolated HT from 1999-2020 were identified using OPTN data and grouped into 3 eras (Era 1: 1999-2006; Era 2: 2006-2016; Era 3: 2016-2020) based on when UNOS revised the heart allocation system. Cox proportional hazards modeling was used to identify factors associated with death or delisting due to deterioration. Overall 11,374 patients met inclusion criteria (3,248 in Era 1; 5,378 in Era 2; 2,748 in Era 3). Waitlist mortality declined significantly across eras (21%, 17%, 13%, P<0.001). The prevalence at listing of major risk factors for mortality declined across eras including a reduction by 47% in ECMO use (11% to 6%, P<0.001), 33% in ventilator use (27% to 18%, P<0.001), 26% in dialysis use (2.5% to 1.8%, P=0.08); in contrast VAD use at listing increased by 243% (6% to 15%, P<0.001). Infant mortality declined significantly (27% to 20%, P<0.001) with a 48% decline in mortality for blood group O patients (relative to the background decline for all blood groups) and a 69% decline in infant VAD mortality (P<0.01). In Era 3, RCM and re-transplant patients not eligible for status 1A without exception had higher mortality than 1A DCM patients on LVAD support (16% vs 5.3%, P<0.01). Pediatric HT waitlist mortality has declined significantly over the past 20 years. There is evidence to suggest that greater VAD use, revisions to organ allocation, refinements in patient selection and ABO-I transplant may all contribute. Organ allocation inefficiencies persist under the current allocation system suggesting opportunities for allocation improvement may still exist.

The Case Number Changes in Adult Heart Transplantation and Waitlist Addition Due to COVID-19

PurposeTo understand the long term effect of COVID-19 on 1) heart transplant waitlist trends and on 2) heart transplant case numbers in the United States.MethodsThe number of new adult heart transplant waitlist additions and transplant procedures were obtained from the UNOS database. Our time frame includes the 52 weeks between September 3, 2019 and September 4, 2020. Temporal changes in waitlist additions and heart transplants were analyzed using interrupted time series analyses with two transition periods. The first transition from the pre-COVID to the post-COVID era was determined as the week of March 11, 2020, when the first state imposed stay-at-home orders. The second transition period was determined as the first state re-opening during the week of April 22, 2020.ResultsWeekly waitlist additions were decreasing at -0.19 additions per week (95% CI: -0.35 to -0.03, p=0.018) prior to the COVID-19 era, defined as before the week of March 11, 2020, with a significant decrease in weekly waitlist additions of -2.09 (95% CI: -2.44 to -1.73, p< 0.001) during the post-COVID-19 era and prior to the first state re-opening the week of April 22, 2020 (Figure A). Weekly waitlist additions increased at 2.16 additions per week (95% CI: 1.81 to 2.51, p<0.001) following the first state announcing re-opening the week of April 22, 2020.Weekly transplants were relatively unstable, although decreasing at -0.003 transplants per week (95% CI: -0.279 to 0.273, p=0.984) in the pre-COVID era, and were trending downward at -0.18 transplants per week (95% CI: -0.3702 to 0.0036, p=0.054) thereafter (Figure B). The number of transplants rebounded and increased significantly at 0.49 transplants per week (95% CI: 0.26 to 0.72, p<0.001) after April 22, 2020.ConclusionThe number of heart transplants and waitlist additions decreased significantly due to COVID-19 and rebounded following the first US state reopening the week of April 22, 2020. Waitlist additions continue to rise past levels observed during the pre-COVID era.

Heart Transplant Waitlist Outcomes and Wait Time by Center Volume: Where Should You List?

Purpose With new devices and policy changes in the heart transplantation, patients are faced with increasingly complex management options. Among one of the decisions they must make is which transplant center they can and should list under. Here we explored waitlist outcomes by transplant center volume. Methods We performed a retrospective analysis of adults listed for primary heart transplantation from 2008 to 2018 using the UNOS Database. Transplant centers were split into low ( 30 HTx/year) volume. Multivariable Cox Proportional Hazards analysis identified predictors of death prior to transplantation; Cox model was adjusted for age at listing, transpulmonary gradient, and use of LVAD while on the waitlist. Results Of the 37,779 patients included in our study, only 24,285 (64.3%) underwent transplantation. Of the remaining 13,494, 6,687 (49.6% of non-transplanted patients) died before receiving transplantation. Of the 140 centers, 51 were low volume (1,412 HTx), 64 were medium volume (11,687 HTx), and 25 were high volume (11,186 HTx); 118 patients were listed at centers which did not perform any transplants in the years analyzed. LVAD utilization (at listing or while listed) was 20.2% for low, 31.8% for medium, and 25.1% for high volume centers. Of the 3,192 patients listed in low-volume centers, only 1,412 (44.2%) underwent transplantation, while 800 (25.1%) died prior to transplant; of the 18,538 listed in medium volume centers, 11,687 (63.0%) underwent transplantation, while 3,343 (18.0%) died prior to transplant; of the 15,931 listed in high volume center, 11,186 (70.2%) underwent transplantation, while 2,503 (15.7%) died prior to transplant. Average time on waitlist was 328.7 + 453.7 days for low-volume, 358.5+469.8 for medium-volume, and 313.7+484.6 for high-volume centers (p = NS). Cox proportional hazards analysis demonstrated listing at a higher volume center to be an independent predictor of lower death rate while on transplant waitlist (HR 0.89, P Conclusion Survival to transplantation was higher for patients listed in higher volume centers. This may be associated with higher utilization rates of LVADs which was also associated with improved waitlist outcomes, or possibly better management of advanced heart failure in centers more experienced with this patient population.

Berlin Heart Explantation Systematic Approach Protocol in a Single Center Experience

Introduction Berlin Heart EXCOR ventricular assist device (VAD) implantation in children is widely used as a bridge-to-heart transplantation. VAD support as a bridge-to-recovery is rare. There is scarcity of literature describing systematic evaluation of cardiac recovery employed in VAD explanation in children. Case Report A 13 month-old boy presented to the emergency department with acute congestive heart failure secondary to myocarditis. Echocardiogram demonstrated severely depressed left ventricular (LV) function with severe mitral regurgitation. He developed ventricular tachycardia with hemodynamic compromise necessitating institution of veno-arterial extracorporeal membranous oxygenation (ECMO). He was decannulated 11 days later after a successful trial off, but due to no further improvement in cardiac status, he underwent Berlin Heart EXCOR LVAD placement as a bridge-to-transplant. After 3 months of VAD support, we noted evidence of myocardial recovery and discussed the possibility of VAD explant. A weaning protocol was developed that consisted of two phases. The first phase consisted of a trial off with echocardiographic monitoring of biventricular function, atrioventricular valve regurgitation and LV diastolic dimension. The second phase was performed one week later in the cardiac catheterization suite, while monitoring hemodynamic measurements at baseline and with manual pumping followed by dobutamine challenge at the end of trial off. Clinical data was satisfactory and patient met established goals to undergo explant. Berlin explantation was succesfully performed the following day. His recovery was unremarkable and was discharged 2 weeks after explant. Patient was seen for follow-up at 1, 2 and 3 months post-discharge and he is doing well. Summary We established guidelines for trialing off VAD support to maximize the identification of potential candidates for VAD explantation. This protocol includes three main stages: screening, trial-off with echocardiography and trial-off in the catheterization suite. This case demonstrates that myocardial recovery can take longer than previously recognized in children with myocarditis and it highlights that strong consideration should be given to patients with a stable VAD course to remain inactive on the heart transplant waitlist to allow time for myocardial recovery and successful explantation.

Role of implantable cardioverter-defibrillator in patients awaiting heart transplant in the continuous-flow left ventricular assist device era.

Implantable cardioverter-defibrillators (ICDs) have been shown to have survival advantage in advanced heart failure patients. Few studies have evaluated the role of ICDs in patients supported with continuous-flow left ventricular assist devices (CFVADs). We aimed to evaluate the impact of ICD and CFVAD on heart transplant (HTx) waiting list survival. We queried the United Network for Organ Sharing (UNOS) thoracic transplant database between years 2007 and 2016 for patients aged ≥ 18 years listed for HTx. Patients receiving devices other than CFVAD were excluded. Patients were divided into groups-with and without CFVAD and further subdivided into groups-with and without ICD use. Kaplan-Meier curves were used to evaluate the survival outcomes. There were 34860 patients listed for HTx during study period of which 11481 (32%) had a CFVAD and 26139 (75%) had an ICD. Within CFVAD group, patients with ICD were older, more likely male, with higher creatinine and listed as UNOS status 1A. In the No-CFVAD group, 1-year waitlist survival was significantly better with ICD use (81% vs. 73%, P < .0001); however, in CFVAD patients, 1-year survival with ICD use was comparable to No-ICD use (95% vs. 94%, P = .1). Use of ICD is associated with significantly better heart transplant waitlist survival in patients not supported by CFVAD. In patients supported with CFVAD, the ICD does not offer additional survival benefit.

Increased frequency of heart transplantation, shortened waitlist time and preserved post-transplant survival in adults with congenital heart disease, on the new heart transplant allocation system.

Historically, adult congenital patients have longer waitlist time and worse outcomes on the heart transplant waitlist as well as poorer early post-transplant survival. A new heart transplantation allocation system was implemented in the United States on October 18, 2018. The effect of the new allocation system on adult congenital patients is unknown. Adult congenital patients listed for transplantation between November 1, 2015 and September 30, 2019 registered in the United Network for Organ Sharing were included in the study. October 18, 2018 was used as the limit to distribute listed and transplanted patients into old and new groups. A total of 399 patients were listed for heart transplant only, 284 in the old system and 115 in the new system. Clinical characteristics were similar between both groups. The cumulative incidence of poor outcome on the transplant list was similar in both groups (P=.23), but the cumulative incidence of transplant was higher in the new system group (P<.009) and was associated with a shorter waitlist time. The one-year post-transplant outcome was similar between old and new groups (P=.37). The new allocation system has benefited adult congenital patients with increased cumulative frequency of transplantation without worsening short-term survival after transplantation.