Black Heart Transplant Recipients Research Articles

Is the Affordable Care Act Moving the Needle for Advanced Heart Failure Therapies for Black Patients?

Is the Affordable Care Act Moving the Needle for Advanced Heart Failure Therapies for Black Patients?

Racial disparities in post-transplant stroke and mortality following stroke in adult cardiac transplant recipients in the United States.

Black heart transplant recipients have a higher mortality rate than white recipients 6-12 months after transplant. Whether there are racial disparities in post-transplant stroke incidence and all-cause mortality following post-transplant stroke among cardiac transplant recipients is unknown. Using a nationwide transplant registry, we assessed the association between race and incident post-transplant stroke using logistic regression and the association between race and mortality among adults who survived a post-transplant stroke using Cox proportional hazards regression. We found no evidence of an association between race and the odds of post-transplant stroke (OR = 1.00, 95% CI: 0.83-1.20). The median survival time of those with a post-transplant stroke in this cohort was 4.1 years (95% CI: 3.0, 5.4). There were 726 deaths among the 1139 patients with post-transplant stroke, including 127 deaths among 203 Black patients and 599 deaths among 936 white patients. Among post-transplant stroke survivors, Black transplant recipients experienced a 23% higher rate of mortality compared to white recipients (HR = 1.23, 95% CI: 1.00-1.52). This disparity is strongest in the period beyond the first 6 months and appears to be mediated by differences in the post-transplant setting of care between Black and white patients. The racial disparity in mortality outcomes was not evident in the past decade. The improved survival of Black patients in the recent decade may reflect overall protocol improvements for heart transplant recipients irrespective of race, such as advancements in surgical techniques and immediate postoperative care as well as increased awareness about reducing racial disparities.

Abstract 9800: Racial Differences in Donor-Derived and Mitochondrial Cell-Free Dna Could Explain Inferior Outcomes in Black Heart Transplant Patients, on Behalf of the Graft Investigators

Introduction: Black heart transplant patients are at higher risk of acute rejection (AR) and death than White patients. Our group has shown that %donor-derived cell-free DNA (%ddcfDNA) is a sensitive and specific marker of AR in heart transplantation. Cell-free mitochondrial DNA (cfmtDNA) has been linked to allograft dysfunction and may mechanistically implicated in inferior outcomes for Black heart transplant recipients. Hypothesis: Higher levels of allograft injury when quantitated using %ddcfDNA and total cfmtDNA will be seen in Black heart transplant patients as compared to White patients. Methods: The Genomic Research Alliance for Transplantation (GRAfT) is a multicenter, prospective, longitudinal cohort study of heart transplant patients transplanted between 2015 and 2021. We included Black and White patients and shotgun sequencing was used to quantitate %ddcfDNA and polymerase chain reaction (PCR) to quantitate total cfmtDNA levels. AR was defined as grade ≥2R cellular rejection or pAMR ≥1 antibody-mediated rejection (AMR). Results: We included 151 patients (73 Blacks and 78 Whites), the median age was 56y (29% Female sex). Patients of both racial groups had comparable baseline characteristics. There were a ~1100 ddcfDNA and cfmtDNA measures included in the analysis. At 18-months, the incidence of AR was 2.8% in White patients and 9.2% in Black patients (p<0.01). The diagnostic accuracy of %ddcfDNA to detect AR was comparable between Black and White patients (0.90 vs. 0.83, p=0.19). The %ddcfDNA and cfmtDNA was higher at serial time points after transplant in Black compared to White patients (Figure). CfmtDNA levels were also elevated with AMR which occurred almost exclusively in Black patients (No rejection: 146,345 copies/ul, AMR: 242,238 copies/ul; p=0.004). Conclusions: Elevated levels of %ddcfDNA and cfmtDNA after heart transplant may explain the higher incidence of AR, AMR, and inferior outcomes in Black heart transplant recipients.

Post-transplant mortality and graft failure after induction immunosuppression among Black heart transplant recipients in the United States

Black heart transplant recipients are more likely to receive induction immunosuppression compared to other races because of higher rates of acute rejection, graft failure, and mortality. However, it is not known whether contemporary induction immunosuppression improves their post-transplant outcomes. To evaluate whether Black patients who were prescribed induction immunosuppression therapy have lower all-cause mortality or graft-failure rates compared to those who were not, we studied Black U.S. adult heart transplant recipients in the Scientific Registry of Transplant Recipients database (2008-2018). We used multivariable Cox proportional hazards regression analysis to compare the hazards of all-cause mortality or graft failure as a composite, for patients who were prescribed induction immunosuppression and those who were not. Among 5160 recipients, 2787 (54.0%) were prescribed induction immunosuppression and 2373 (46.0%) were not. There was no evidence of survival differences according to induction immunosuppression for the composite of all-cause mortality or graft failure (aHR=1.13, 95% CI 0.96-1.32), mortality (aHR=1.14, 95% CI 0.97-1.34), graft failure (aHR=1.05, 95% CI 0.82-1.34) and acute rejection (aHR=1.00, 95% CI 0.89-1.12). Given the side effects of treatment, future guidelines should reconsider the recommendation for induction immunosuppression among Black patients.

Abstract 11003: Racial Disparities in Induction Immunosuppression Use Among Heart Transplant Recipients in the United States

Introduction: Black heart transplant recipients have higher rates of acute rejection, graft failure, and mortality compared to other races. Induction immunosuppression in the immediate peri-transplant period may lower the risk of acute rejection among high-risk patients, including Black transplant recipients. However, it is not known whether the odds of receiving this treatment are different across races. Therefore, we evaluated whether there are disparities in the use of induction immunosuppression following heart transplants among Black patients compared to other races. Methods: We conducted a cross-sectional study of U.S. adults in the Scientific Registry of Transplant Recipients who received their first heart transplant between 2008 - 2018. We used mixed-effects logistic regression to compare the odds of receiving induction immunosuppression agents (IL-2 receptor antagonists, polyclonal anti-lymphocyte antibodies, and CD52 monoclonal antibodies) across different races. Results: Among 23,935 adult heart transplant recipients, 5,160 (21.6%) were Black, including 2,797 (54.2%) who received induction immunosuppression, and 18,775 (78.4%) were non-Black, including 9,499 (50.6%) who received induction immunosuppression. After accounting for demographic and clinical characteristics and treatment center, Black race was associated with 28% higher odds (Odds Ratio=1.28, 95% CI 1.17-1.40) of induction immunosuppression use compared to other races. Similar results were observed when race was further stratified (Table 1). Conclusions: In our study, Black heart transplant recipients were more likely to receive induction immunosuppression than transplant recipients of other races. However, further research on post-transplant clinical outcomes including survival following induction immunosuppression among Black patients is needed to formulate treatment guidelines.

Better Understanding the Disparity Associated With Black Race in Heart Transplant Outcomes: A National Registry Analysis.

Black heart transplant recipients have higher risk of mortality than White recipients. Better understanding of this disparity, including subgroups most affected and timing of the highest risk, is necessary to improve care of Black recipients. We hypothesize that this disparity may be most pronounced among young recipients, as barriers to care like socioeconomic factors may be particularly salient in a younger population and lead to higher early risk of mortality. We studied 22 997 adult heart transplant recipients using the Scientific Registry of Transplant Recipients data from January 2005 to 2017 using Cox regression models adjusted for recipient, donor, and transplant characteristics. Among recipients aged 18 to 30 years, Black recipients had 2.05-fold (95% CI, 1.67-2.51) higher risk of mortality compared with non-Black recipients (P<0.001, interaction P<0.001); however, the risk was significant only in the first year post-transplant (first year: adjusted hazard ratio, 2.30 [95% CI, 1.60-3.31], P<0.001; after first year: adjusted hazard ratio, 0.84 [95% CI, 0.54-1.29]; P=0.4). This association was attenuated among recipients aged 31 to 40 and 41 to 60 years, in whom Black recipients had 1.53-fold ([95% CI, 1.25-1.89] P<0.001) and 1.20-fold ([95% CI, 1.09-1.33] P<0.001) higher risk of mortality. Among recipients aged 61 to 80 years, no significant association was seen with Black race (adjusted hazard ratio, 1.12 [95% CI, 0.97-1.29]; P=0.1). Young Black recipients have a high risk of mortality in the first year after heart transplant, which has been masked in decades of research looking at disparities in aggregate. To reduce overall racial disparities, clinical research moving forward should focus on targeted interventions for young Black recipients during this period.

Race/Ethnic Disparities in Cardiac Transplantation

Heart transplant (HT) is the therapy of choice for patients with end-stage heart failure (HF), leading to substantial improvements in quality of life, functional status, and longevity compared to optimal medical therapy for end-stage HF. However, race/ethnic disparities in post-HT survival persist and remain a major concern. The purpose of this review is to describe differences in post-transplant outcomes based on race/ethnicity and to highlight evolving knowledge of the reasons for these persistent disparate outcomes. Black HT recipients have the highest risk for allograft failure and the worst survival post-HT compared to other race/ethnic groups. Although differences in socioeconomic status, access to medical care, and medical compliance have been cited in the past as reasons for these disparate outcomes, recent research highlights the importance of heightened immune reactivity in black HT recipients as a major cause of allograft loss and death. Novel techniques such as gene expression profiling, detection of donor specific antibodies, and detection of genotypes associated with increased metabolism of immunosuppressive medications highlight the role of immune and inflammatory dysregulation and reduced immunosuppressive drug efficacy as significant contributors to post-HT outcomes. Race/ethnic disparities in post-HT outcomes are due to a complex interplay of immunologic, clinical, and socioeconomic factors. However, multiple reports that demonstrate that black race confers a survival disadvantage post-HT that is independent of differences in access to care or socioeconomic status highlight the need for more research to understand racial differences in biological and genetic responses to immunosuppressive therapy.

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CARDIAC TRANSPLANTATION IN AFRICAN AMERICANS, A SINGLE CENTER EXPERIENCE

There is limited available data on the subject of patient survival difference between black and non black heart transplant recipients. We hypothesized that there is a higher mortality rate among African American (AA) recipients compared to non AA recipients after cardiac transplantation. We

Persistent racial disparities in survival after heart transplantation.

Racial and ethnic disparities are well documented in many areas of health care, but have not been comprehensively evaluated among recipients of heart transplants. We performed a retrospective cohort study of 39075 adult primary heart transplant recipients from 1987 to 2009 using national data from the United Network of Organ Sharing and compared mortality for nonwhite and white patients using the Cox proportional hazards model. During the study period, 8082 nonwhite and 30 993 white patients underwent heart transplantation. Nonwhite heart transplant recipients increased over time, comprising nearly 30% of transplantations since 2005. Nonwhite recipients had a higher clinical risk profile than white recipients at the time of transplantation, but had significantly higher posttransplantation mortality even after adjustment for baseline risk. Among the nonwhite group, only black recipients had an increased risk of death compared with white recipients after multivariable adjustment for recipient, transplant, and socioeconomic factors (hazard ratio, 1.34; 95% confidence interval, 1.21 to 1.47; P<0.001). Five-year mortality was 35.7% (95% confidence interval, 35.2 to 38.3) among black and 26.5% (95% confidence interval, 26.0 to 27.0) among white recipients. Black patients were more likely to die of graft failure or a cardiovascular cause than white patients, but less likely to die of infection or malignancy. Although mortality decreased over time for all transplant recipients, the disparity in mortality between blacks and whites remained essentially unchanged. Black heart transplant recipients have had persistently higher mortality than whites recipients over the past 2 decades, perhaps because of a higher rate of graft failure.

The differential metabolic impact of tacrolimus and cyclosporine immunosuppression in black heart transplant recipients: hyperlipidemia, hypertension and hyperglycemia

disease in 10, viral cardiomyopathy in 9, hypertrophic cardiomyopathy in 7, congenital heart disease in 6, and others in 14. The follow-up was 3.863.1 years (minimum 2 days, maximum 10.2 years, median 3.1 years). Thirty-day-mortality rate was 5.5%. The 1, 5, and 10-year actuarial survivals were 86%, 75%, and 54%, respectively. Cause of death for the entire group (total 69) were infection in 18(26% of deaths), graft coronary disease in 12(17%), acute rejection in 8(11.6%), stroke in 6(8.7%), malignancy in 4(5.8 %), primary graft failure in 4(5.8%), other causes in 13(18.8%), and unknown in 4(5.8%). Actuarial freedom from acute rejection at 1, 3 months, 1, 5, and 10 years was 64.4%, 54.1%, 43.7%, 40.1%, and 40.1%, respectively. Actuarial freedom from acute rejection-related death at 3 months, 1, 5, and 10 years was 98.2%, 97.7%, 95.4%, and 95.4%, respectively. Actuarial freedom from infection at 1, 3 months, 1, 5, and 10 years was 91.4%, 81.6%, 69.4%, 58.8%, and 54.2%, respectively. Actuarial freedom from infection-related death at 3 months, 1, 5, and 10 years was 96.8%, 93.3%, 91.2%, and 91.2%, respectively. Actuarial freedom from graft coronary artery disease at 1, 5, and 10 years was 95.7%, 72.4%, and 53.0%, respectively. Actuarial freedom from graft coronary artery disease-related death or retransplantation at 1, 5, and 10 years were 99.5%, 93.7%, and 85.3%, respectively. CONCLUSION: These data suggested satisfactory long-term results of adult cardiac transplantation utilizing FK506.

A randomized comparison of an immunosuppressive strategy using tacrolimus and cyclosporine in black heart transplant recipients

A randomized comparison of an immunosuppressive strategy using tacrolimus and cyclosporine in black heart transplant recipients