Racial and ethnic differences in wait-list outcomes in patients listed for heart transplantation in the United States.

BACKGROUND: Racial differences in long-term survival after heart transplant (HT) are well known. We sought to assess racial/ethnic differences in wait-list outcomes among patients listed for HT in the United States in the current era. METHODS AND RESULTS: We compared wait-list and posttransplant in-hospital mortality among white, black, and Hispanic patients ≥ 18 years of age listed for their primary HT in the United States between July 2006 and September 2010. Of 10 377 patients analyzed, 71% were white, 21% were black, and 8% were Hispanic. Black and Hispanic patients were more likely to be listed with higher urgency (listing status 1A/1B) in comparison with white patients (P<0.001). Overall, 10.5% of white, 11.6% of black, and 13.4% of Hispanic candidates died on the wait-list or became too sick for a transplant within 1 year of listing. After adjusting for baseline risk factors, Hispanic patients were at higher risk of wait-list mortality (hazard ratio 1.51, 95% CI 1.23, 1.85) in comparison with white patients, but not black patients (hazard ratio 1.13, 95% CI 0.97, 1.31). In comparison with white HT recipients, posttransplant in-hospital mortality was higher in black recipients (odds ratio 1.53, 95% CI 1.15, 2.03) but was not different in Hispanic recipients (odds ratio 0.78, 95% CI 0.48, 1.29). CONCLUSIONS: Hispanic patients listed for HT in the United States appear to be at higher risk of dying on the wait-list or becoming too sick for a transplant in comparison with white patients. Black patients are not at higher risk of wait-list mortality, but they have higher early posttransplant mortality.

The relationship of socio-demographic factors and satisfaction with social support at five and 10 yr after heart transplantation.

BACKGROUND: Despite the fact that social support has been found to be important to cardiovascular health, there is a paucity of information regarding the relationship between social support and outcomes long term after heart transplantation (HT). The purposes of this study were to examine demographic and psychosocial characteristics and their relationship to social support after HT and to identify whether socio-demographic variables are predictors of satisfaction with social support post-HT. METHODS: Data were collected from 555 HT patients (pts) (78% men, 88% white, mean age = 53.8 yr at time of transplant) at four US medical centers using the following instruments: Social Support Index, QOL Index, HT Stressor Scale, Jalowiec Coping Scale, Sickness Impact Profile, Cardiac Depression Scale, and medical records review. Statistical analyses included t-tests, correlations, and linear and multivariate regression. RESULTS: There were no associations between education and ethnicity and perception of social support at five and 10 yr after HT. Married and older pts reported higher satisfaction with social support after HT. Being married and having higher education were predictors of better overall satisfaction with social support at 10 yr post-heart transplantation. CONCLUSIONS: Knowledge of relationships between socio-demographic factors and social support may assist clinicians to address social support needs and resources long term after HT.

Persistent racial disparities in survival after heart transplantation.

BACKGROUND: Racial and ethnic disparities are well documented in many areas of health care, but have not been comprehensively evaluated among recipients of heart transplants. METHODS AND RESULTS: 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. CONCLUSIONS: 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.

Association of race and socioeconomic position with outcomes in pediatric heart transplant recipients.

We assessed the association of socioeconomic (SE) position with graft loss in a multicenter cohort of pediatric heart transplant (HT) recipients. We extracted six SE variables from the US Census 2000 database for the neighborhood of residence of 490 children who underwent their primary HT at participating transplant centers. A composite SE score was derived for each child and four groups (quartiles) compared for graft loss (death or retransplant). Graft loss occurred in 152 children (122 deaths, 30 retransplant). In adjusted analysis, graft loss during the first posttransplant year had a borderline association with the highest SE quartile (HR 1.94, p = 0.05) but not with race. Among 1-year survivors, both black race (HR 1.81, p = 0.02) and the lowest SE quartile (HR 1.77, p = 0.01) predicted subsequent graft loss in adjusted analysis. Among subgroups, the lowest SE quartile was associated with graft loss in white but not in black children. Thus, we found a complex relationship between SE position and graft loss in pediatric HT recipients. The finding of increased risk in the highest SE quartile children during the first year requires further confirmation. Black children and low SE position white children are at increased risk of graft loss after the first year.

Disparate distribution of 16 candidate single nucleotide polymorphisms among racial and ethnic groups of pediatric heart transplant patients.

BACKGROUND: Allograft failure in African-Americans remains higher than in Caucasians. Single nucleotide polymorphisms (SNPs) have been associated with altered allograft outcomes. METHODS: In this multi-center study we compared SNP frequencies in 364 pediatric heart recipients from three ethnic/racial groups: Caucasian (n = 243), African-American (n = 39), and Hispanic (n = 82). The target genes were: tumor necrosis factor-alpha, interleukin (IL)-10, IL-6, interferon (IFN)-gamma, vascular endothelial growth factor (VEGF), transforming growth factor-beta1, Fas, FasL, granzyme B, ABCB1, CYP3A5. RESULTS: Compared to Caucasians, African-Americans exhibited a higher prevalence of genotypes associated with low expression of IFN-gamma (24% vs. 45.7%, P < 0.001) and IL-10 (33% vs. 57.1%, P = 0.052). African-Americans also exhibited an increased prevalence of high IL-6 (82.9% vs. 38.1%; P < 0.001). VEGF -2578 C/C and -460 C/C genotypes were found more frequently in African-Americans and Hispanics as compared to Caucasians (P < 0.001). G/G genotype of Fas and T/T genotype of FasL were expressed more often by African-American recipients. The prevalence of Granzyme B (-295A/G) genotype was differentially distributed in the three groups. Compared with Caucasians, African-Americans were twice as likely to carry the ABCB1 2677 G/G genotype (78.6% vs. 33.7%, P < 0.0025), and they were more frequent carriers of the CYP3A5 *1/*1 genotype (35.7% vs. 0.6% in Caucasians and 7.2% in Hispanics; P < 0.001). CONCLUSION: African-Americans have a genetic background that may predispose to proinflammatory/lower regulatory environment, reduced drug exposure and immunosuppressive efficacy. In this ongoing multicenter study, these gene polymorphisms differences among ethnic/racial groups are being documented so that therapeutic strategies can be devised to optimize outcomes for pediatric transplant recipients.

The path not taken: social and cultural barriers to thoracic transplantation.

Religious beliefs, misperceptions, and distrust of the health care system have been cited as barriers to organ donation or transplantation in minorities. Improved training of hospital staff on donation protocols has been demonstrated to increase consent rates for or-gan donation. Increased interaction of minorities with ethnically appropriate transplant candidates, recipients, and donation or procurement personnel has a positive effect on donor rates. Programs using such practices must be expanded to overcome significant barriers to the transplantation of solid organs. Research into additional ways to improve acceptance of organ transplantation by minorities is needed to increase participation rates.

Is there racial disparity in outcomes after solid organ transplantation?

BACKGROUND: We sought to determine if disparities in survival and health-related quality of life (HRQOL) occurred after solid organ transplantation at our institution. METHODS: Data were extracted from a database including information regarding transplants that took place from 1990 to 2002. The HRQOL was assessed in patients by using the Karnofsky functional performance (FP) index and the Medical Outcomes Study Short Form 36 (SF-36) questionnaire. RESULTS: Data were collected on recipients of liver (n = 413), heart (n = 299), kidney (n = 892), and lung (n = 156). Blacks represented a minority of recipients: liver 7%, heart 8%, kidney 23%, and lung 6%. There were no statistically significant differences in patient survival between blacks and whites. Graft survival differed in kidney only with a 5-year survival: 72% for blacks versus 79% for whites (P <0.001). The FP and HRQOL improved (P <0.05) after transplantation in both groups. There were no differences on measures of the FP or HRQOL. CONCLUSIONS: Blacks had comparable survival and improvement in FP and HRQOL in comparison with whites.

Evidence for racial disparity in cardiac transplantation survival rates.

Studies show that survival rates of cardiac transplantation are lower for African American transplant recipients than for Caucasians. Due to similarities in terms of etiology, treatment modalities and responses to these modalities, the authors examine some potential variables for survival of cardiac transplantation that have been well documented in both the renal transplantation literature and the medically managed congestive heart failure literature. The authors also discuss access to care, socioeconomic factors and immunological differences in attempting to identify relevant factors for survival of cardiac transplantation.

Heart transplantation in Japan: a critical appraisal for the results and future prospects.

As of September 30, 2011, a total of 113 patients with end-stage heart failure underwent heart transplantation in Japan, and the early and late (10 years) survival rates appear better than those reported in 2011 by the Registry of the International Society of Heart and Lung Transplantation (ISHLT). Among the risk factors determining survival, use of both left ventricular assist devices (LVADs) during the pretransplant care and marginal donor hearts increased the risk while factors favoring survival included younger adult recipients and fewer patients with ischemic cardiomyopathy; factors noted in Japanese patients in comparison with those registered in the ISHLT report. Although only a few patients have reached 10 years follow-up, so far none has died or required retransplantation due to cardiac allograft vasculopathy (CAV). CAV may develop later in Japanese heart transplant patients than in those of mixed inter-ethnic transplants. Recently, survival rates with newer LVADs have dramatically improved and therefore, selection criteria for the permanent or destination use of an LVAD or for heart transplantation require further evaluation, depending upon the various factors in candidates with profound heart failure.

Cardiac transplantation in the United States from 1988 to 2010: an analysis of OPTN/ UNOS registry.

We examined heart transplant demographics, graft outcomes and associated risk factors in the United States from 1988 to 2010, reported in the UNOS registry. Only those who underwent primary orthotopic heart transplants were selected, excluding those with multi-organ transplants. Infant mortality in the first three months after heart transplantation should be given more attention because strategies to prevent early graft failure would have the greatest impact on survival in this group. African American recipients are the group most vulnerable to graft loss in solid organ transplantation, with no exception for heart transplant. Since we found that matching AA recipients with AA donors significantly raises the survival rate, race-matching should be advocated for this group. HLA compatibility does play an independent role in heart transplantation, although the effect is not as obvious as in kidney transplantation.

Improved survival in heart transplant recipients in the United States: racial differences in era effect.

BACKGROUND: Posttransplant survival in heart transplant recipients has progressively improved during the past 2 decades. It is unknown, however, whether the major racial groups in the United States have benefited equally. METHODS AND RESULTS: We analyzed all primary heart transplant recipients aged ≥18 years in the United States from 1987 to 2008. We compared posttransplant survival in white, black, and Hispanic recipients in 5 successive eras (1987 to 1992, 1993 to 1996, 1997 to 2000, 2001 to 2004, 2005 to 2008). Early survival was defined as freedom from death or retransplantation during the first 6 months posttransplant. Longer-term, conditional survival was assessed in patients who survived the first 6 months. There were 29 986 (81.6%) white, 4745 (12.9%) black, and 2017 (5.5%) Hispanic patients in the study cohort. Black patients were at increased risk of early death or retransplant (hazard ratio [HR], 1.15; 95% CI, 1.05 to 1.26) in adjusted analysis. Early posttransplant survival improved (HR, 0.83; 95% CI, 0.80 to 0.87 for successive eras) equally in all 3 groups (black-era interaction, P=0.94; Hispanic-era interaction, P=0.40). Longer-term survival improved in white (HR, 0.95; 95% CI, 0.92 to 0.97 for successive eras) but not in black (HR, 1.04; 95% CI, 0.99 to 1.09) or Hispanic (HR, 1.02; 95% CI, 0.95 to 1.09) recipients, resulting in increased disparities in longer-term survival with time. CONCLUSIONS: Early posttransplant survival has improved equally in white, black, and Hispanic heart transplant recipients. Longer-term survival has improved in white but not in black or Hispanic recipients, resulting in a more marked disparity in outcomes in the current era. These disparities warrant further investigation and targeted interventions.

Common occurrence of everolimus-associated aphthous stomatitis in Japanese heart transplant recipients.

Mammalian target of rapamycin (mTOR) inhibitors display antiproliferative effects with less nephrotoxicity than calcineurin inhibitors. However, clinical use of mTOR inhibitors can be associated with a series of adverse events. We experienced cases of aphthous stomatitis associated with everolimus (EVL) in four Japanese heart transplant recipients treated at the target trough EVL blood level after a switch from mycophenolate mofetil between April and December 2007. All four patients developed aphthous stomatitis; three required reduction of the exposure and one, EVL discontinuation due to stomatitis as well as other side effects. All patients recovered from stomatitis after reduction or withdrawal of EVL. Thus, we considered that EVL-related stomatitis might occur commonly among the Japanese population. The proper dosage, effects, and frequency of the side effects of mTOR inhibitors may vary by ethnic population.

Comparison across races of peak oxygen consumption and heart failure survival score for selection for cardiac transplantation.

The aim of the present study was to determine whether peak oxygen consumption (VO(2)) and the Heart Failure Survival Score (HFSS) predict prognosis in European-American, African-American, and Hispanic-American patients with chronic heart failure referred for heart transplantation. The peak VO(2) and the HFSS have previously been shown to effectively risk stratify patients with chronic heart failure and are criteria for the listing for heart transplantation. However, the effect of race on the predictive value of these variables has not been studied. A total of 715 patients with congestive heart failure (433 European American, 126 African American, 123 Hispanic American, and 33 other), who had been referred for heart transplantation, underwent cardiopulmonary exercise testing with measurement of the peak VO(2) and calculation of the HFSS. A total of 354 patients had died or undergone urgent heart transplantation or implantation of a left ventricular assist device during the 962 +/- 912 days of follow-up. On univariate and multivariate Cox hazard analysis, both peak VO(2) and the HFSS were powerful prognostic markers in the overall cohort and in the separate races. In the receiver operating characteristic curve analysis, the areas under the curve at 1 and 2 years of follow-up were greater for the HFSS than for peak VO(2). In conclusion, HFSS and peak VO(2) can be used for transplant selection; however, in the era of modern therapy and across races and genders, the HFSS might perform better than the peak VO(2).

Donor-recipient race mismatch and graft survival after pediatric heart transplantation.

BACKGROUND: Black recipient race has been shown to predict poorer graft survival after pediatric heart transplantation. We analyzed our single-center experience comparing graft survival by race and the impact of donor-recipient race mismatch. METHODS: One hundred sixty-nine consecutive primary pediatric heart transplant patients were analyzed by donor and recipient race (white recipient, 99; black recipient, 60; other, 10). The groups were similar in preoperative characteristics. There were fewer donor-recipient race matches in blacks compared with whites (10 versus 71; p < 0.0001). RESULTS: Although 30-day and 6-month graft survival was similar for black and white recipients (93.9% and 85.8% versus 93.3% and 83.3%, respectively), overall actuarial graft survival was significantly lower in blacks (p < 0.019). Blacks tended to have a higher incidence of positive retrospective crossmatch (n = 26, 43%) than whites (n = 29, 29%), but this was not statistically significant (p = 0.053). The median graft survival for black recipients was 5.5 years compared with 11.6 years for whites. Donor-recipient race mismatch predicted poorer graft survival (5-year graft survival 48.9% versus 72.3%; p = 0.0032). The median graft survival for donor-recipient race-matched patients was more than twice that for mismatched patients (11.6 years versus 4.4 years). Cox proportional hazard analysis showed that donor-recipient race mismatch neutralized the effect of race on graft survival. CONCLUSIONS: Graft survival after pediatric heart transplantation is inferior for black recipients compared with white recipients. These differences may be explained by a high incidence of donor-recipient race mismatch, which also predicts poorer outcome for all racial groups with pediatric heart transplantation. These data may have implications for future donor allocation schemes.

Socioeconomic position and graft failure in pediatric heart transplant recipients.

BACKGROUND: Socioeconomic (SE) position may affect availability of resources, health-related behavior, and outcomes. We assessed whether patient SE position, determined for the block group of patient residence (average population 1000, smallest census unit with SE data), is associated with graft failure in pediatric heart transplant recipients. METHODS AND RESULTS: We used the US Census 2000 database to derive a composite SE score for the block group of residence for all patients who underwent their first heart transplant at Children's Hospital Boston between 1991 and 2005 (n=135). Cox proportional hazards models were used to determine the risk of graft failure (death or retransplant) in the lowest tertile SE group (low SE group) compared with the remaining 2 of 3 patients (controls). The 2 groups were similar with respect to age, gender, diagnosis, and year of transplant. White race was less frequent in low SE group (64% versus 90%, P=0.001). Graft failure occurred in 46 transplant recipients (40 deaths, 6 retransplant). Low SE group (hazard ratio 2.4, 95% CI 1.3 to 4.3) and nonwhite race (hazard ratio 2.7, 95% CI 1.4 to 5.2) were both associated with higher risk of graft failure. In a multivariable model controlling for diagnosis and pretransplant support, race, and low SE position (hazard ratio 2.0, 95% CI 1.0 to 3.7, P=0.04) remained associated with graft failure. Low SE position group had a higher incidence rate of graft rejection and was at a higher risk of late rejection. CONCLUSIONS: Low SE position may be an independent risk factor for graft failure in pediatric heart transplant recipients.

Utility of the Cylex assay in cardiac transplant recipients.

BACKGROUND: Although the Cylex immune assay has been proposed as a means of tailoring immunosuppression after organ transplantation, there are limited data regarding its utility in cardiac transplant recipients. Therefore, we sought to determine the utility of the Cylex assay in assessing the risk of infection or rejection in cardiac transplant recipients. METHODS: This study is a retrospective review of the clinical course of all adult cardiac transplant recipients who underwent a Cylex assay at UT Southwestern Medical Center between January 2004 and September 2007. RESULTS: One hundred eleven patients were free of significant rejection or infection at the time of the first Cylex assay. Most patients (92%) were >1 year post-transplant. Over the next 157 +/- 41 (mean +/- SD) days, 2 patients had 3 episodes of rejection requiring therapy and 7 patients had 8 infections requiring therapy. The Cylex responses ranged from 17 to 894 ng/ml. No correlation was observed between the baseline Cylex response and subsequent risk of either infection or rejection within 6 months. Lower white blood cell count and African American ethnicity were correlated with a lower Cylex response. CONCLUSIONS: In this study, the Cylex assay had limited utility as an adjunct to routine clinical evaluation in assessing risk of infection or rejection in cardiac transplant recipients.

Cardiac transplantation in the United States: an analysis of the UNOS registry.

Cardiac transplantation is an important option to those with end-stage heart disease. About 2,000 heart transplants are performed each year in the United States. This number has remained relatively stable due to a lack of donors. The major indications for cardiac transplant were coronary artery disease and dilated cardiomyopathy, but over the past 20 years, dilated cardiomyopathy has supplanted coronary artery disease as the major cause. Survival rates have improved with the advent of newer immunosuppressive agents (tacrolimus and mycophenolate). The median survival for 43,906 heart transplants was approximately 9 years. At 20-years the survival rate continued to decline to reach < 10%. Seven-year survival rates for heart transplant recipients transplanted between 1998-1994, 1995-2000, and 2000-2007 were 59%, 62% and 65%, respectively. Infant heart recipients (less than one year old) had poor survival rates during the first post-transplant year (74% compared to > 85% for all other age groups), but those who survived had better long-term outcomes than adults. Elderly recipients (aged 65 or older) had survival rates comparable to younger patients through about 8 years, when survival rates began to fall more rapidly. The long-term success of cardiac transplants still has room for improvement.

Utility of long-term surveillance endomyocardial biopsy: a multi-institutional analysis.

BACKGROUND: The utility of long-term endomyocardial biopsy surveillance in heart transplant recipients has been questioned. This study was undertaken to identify risk factors for late rejection and to examine the impact of different biopsy surveillance protocols on outcomes using the registry of the Cardiac Transplant Research Database. METHODS: The study group consisted of all adult patients who underwent heart transplantation at the 33 centers participating in this investigation between January 1, 1993 and January 1, 2002, survived past the second post-transplant year, and were followed-up by a defined surveillance biopsy protocol. RESULTS: During a follow-up that consisted of 24,137 patient-years, 1,626 late rejections occurred. Shorter time since transplant, history of rejection, younger age and African-American ethnicity of the recipient were strong risk factors for late rejection. The practice of surveillance biopsy varied among institutions. Continued surveillance increased the rate of diagnosis of late rejection (RR = 1.3, p = 0.002). There was no reduction in the incidence of hemodynamically compromising rejection and no increase in survival in patients with long-term vs intermediate-term surveillance. Short-term surveillance was associated with an increased incidence of hemodynamically compromising rejection, particularly among high-risk patients, and increased mortality in African-American patients. CONCLUSIONS: There are no apparent benefits from surveillance biopsy beyond 5 years post-transplant. Surveillance biopsy between 2 and 5 years post-transplant was found to reduce mortality in African-American recipients. Non-African-American recipients at high risk for late rejection will likely benefit from surveillance up to 5 years post-transplant.

Disparities in outcome for black patients after pediatric heart transplantation.

OBJECTIVE: To examine the relationship of black race to graft survival after heart transplantation in children. STUDY DESIGN: United Network for Organ Sharing records of heart transplantation for subjects <18 years of age from 1987 to 2004 were reviewed. Analysis was performed using proportional hazards regression controlling for other potential risk factors. RESULTS: Of the 4227 pediatric heart transplant recipients, 717 (17%) were black. The 1-year graft survival rate did not differ among groups; however, the 5-year graft survival rate was significantly lower for black recipients, 51% versus 69%, P < .001. The median graft survival for black recipients was 5.3 years as compared with 11.0 years for other recipients. Black recipients had a greater number of human leukocyte antigen mismatches, lower median household income, and a greater percentage with Medicaid as primary insurance, P < .001, P < .001, and P < .001. After adjusting for economic disparities, black race remained significantly associated with graft failure, odds ratio = 1.67 (95% CI 1.47 to 1.87), P < .001. CONCLUSIONS: Median graft survival after pediatric heart transplantation for black recipients is less than half that of other racial groups. These differences do not appear to be related primarily to economic disparities.

Social adaptation after cardiothoracic transplantation: a review of the literature.

From the earliest days of transplantation, research has contributed to our knowledge of the psychosocial sequelae associated with the outcomes of the procedure. The purpose of this review is to describe the social adaptation literature for heart, lung, and heart-lung recipients. Social adaptation refers to employment and performance of social roles and responsibilities. Employment research focused on vocational rehabilitation, physical health restoration, and return to work. Social roles and responsibilities research focused on social roles, family relationships, social support, and psychosocial adjustment. Predictors, interventions, and their associations with outcomes are discussed.