Heart transplantation in patients from socioeconomically distressed communities.

BACKGROUND: Studies examining heart transplantation disparities have focused on individual factors such as race or insurance status. We characterized the impact of a composite community socioeconomic disadvantage index on heart transplantation outcomes. METHODS: From the Scientific Registry of Transplant Recipients (SRTR), we identified 49,340 primary, isolated adult heart transplant candidates and 32,494 recipients (2005-2020). Zip code-level socioeconomic disadvantage was characterized using the Distressed Community Index (DCI: 0-most prosperous, 100-most distressed) based on education, poverty, unemployment, housing vacancies, median income, and business growth. Patients from distressed communities (DCI ≥ 80) were compared to all others. RESULTS: Patients from distressed communities were more often non-white, less educated, and had public insurance (all p < 0.01). Distressed patients were more likely to require ventricular assist devices at listing (29.4 vs 27.1%) and before transplant (44.8 vs 42.0%, both p < 0.001), and they underwent transplants at lower-volume centers (23 vs 26 cases/year, p < 0.01). Distressed patients had higher 1-year waitlist mortality or deterioration (12.3% [95% confidence interval (CI) 11.6-13.0] vs 10.9% [95% CI 10.5-11.3]) and inferior 5-year survival (75.3% [95% CI 74.0-76.5] vs 79.5% [95% CI 79.0-80.0]) (both p < 0.001). After adjustment, living in a distressed community was independently associated with an increased risk of waitlist mortality or deterioration hazard ratio (HR 1.10, 95% CI 1.02-1.18) and post-transplant mortality (HR 1.13, 95% CI 1.06-1.20). CONCLUSIONS: Patients from socioeconomically distressed communities have worse waitlist and post-transplant mortality. These findings should not be used to limit access to heart transplantation, but rather highlight the need for further studies to elucidate mechanisms underlying the impact of community-level socioeconomic disparity.

Assessment and management of allosensitization following heart transplant in adults.

Immunological injury to the allograft, specifically by antibodies to de novo donor specific human leukocyte antigen (dnDSA) and antibody mediated injury and rejection are the major limitations to graft survival after heart transplantation (HT). As such, our approach to allosensitization remains limited by the inability of contemporaneous immunoassays to unravel pathogenic potential of dnDSA. Additionally, the role of dnDSA is continuously evaluated with emerging methods to detect rejection. Moreover, the timing and frequency of dnDSA monitoring for early detection and risk mitigation as well as management of dnDSA remain challenging. A strategic approach to dnDSA employs diagnostic assays to determine relevant antibodies in conjunction with clinical presentation and injury/rejection of allograft to tailor therapeutics. In this review, we aim to outline contemporary knowledge involving detection, monitoring and management of dnDSA after HT. Subsequently, we propose a diagnostic and therapeutic approach that may mitigate morbidity and mortality while balancing adverse reactions from pharmacotherapy.

Trainee experience on ischemic times and outcomes following orthotopic heart transplantation.

OBJECTIVE: This study was designed to evaluate the association of surgical training on outcomes following orthotopic heart transplantation in all levels of cardiothoracic surgery fellows. METHODS: A retrospective cohort analysis was performed on all heart transplants at a single institution from 2011 to 2020. Transplants performed using organ preservation systems (n = 10) or with significant missing data were excluded (n = 37), resulting in 154 transplants performed by faculty surgeons and 799 total transplants performed by first-year Accreditation Council for Graduate Medical Education fellows (n = 73), second-year Accreditation Council for Graduate Medical Education fellows (n = 124), or non-Accreditation Council for Graduate Medical Education fellows (n = 602) in a transplantation and mechanical circulatory support fellowship. Primary outcome was warm ischemic time analyzed by year of fellowship. Additional secondary outcomes included 30-day mortality, primary graft dysfunction, reoperation for bleeding, and 5-year survival. Median follow-up was 3 years (interquartile range [IQR], 1.0-5.5 years) and 100% complete. RESULTS: The median number of transplants performed was 30 (IQR, 19.5-51.8) during the study period performed by 22 trainees. Baseline transplant characteristics performed were similar amongst the trainee years, although the first-year Accreditation Council for Graduate Medical Education fellows approached significantly fewer re-do transplants (1.4% vs 8.1% and 4.3%; P = .07). Warm ischemic time was lower in the first-year fellows (49 minutes; IQR, 42-63 minutes) versus second-year fellows (56.5 minutes; IQR, 45.5-69 minutes) and mechanical circulatory support/transplant fellows (56 minutes; IQR, 46-67 minutes) (P = .028). Crossclamp time was also lower in the first-year fellows than in second-year and mechanical circulatory support/transplant fellows, respectively (79 minutes; IQR, 65-100 minutes vs 147 minutes; IQR, 125-176 minutes and 143 minutes; IQR, 119-175 minutes) (P = .008). Secondary outcomes, including 30-day mortality (4.1% [n = 3] vs 2.4% [n = 3] vs 2.7% [n = 16]; P = .76), primary graft dysfunction (5.5% [n = 4] vs 4.0% [n = 5] vs 4.3% [n = 26]; P = .88), reoperation for bleeding (2.7% [n = 2] vs 4.8% [n = 6] vs 4.2% [n = 25]; P = .78), and 5-year survival (82.2%; 95% CI, 66.7%-84.9% vs 77.3%; 95% CI, 66.7%-84.9% vs 79.3%; 95% CI, 74.9%-83.1%; P = .84) were comparable in all groups. CONCLUSIONS: This cohort of nearly 800 operations demonstrates that orthotopic heart transplantation may be performed by cardiac fellowship trainees all levels of training with acceptable short- and long-term outcomes.

The Impact of a High-risk Psychosocial Assessment on Outcomes After Durable Mechanical Circulatory Support.

Patient adherence is vital to the success of durable mechanical circulatory support (MCS), and the pre-MCS assessment of adherence by the multidisciplinary advanced heart failure team is a critical component of the evaluation. We assessed the impact of a high-risk psychosocial assessment before durable MCS implantations on post-MCS outcomes. Between January 2010 and April 2018, 319 patients underwent durable MCS at our center. We excluded those who died or were transplanted before discharge. The remaining 203 patients were grouped by pre-MCS psychosocial assessment: high-risk (26; 12.8%) versus acceptable risk (177; 87.2%). We compared clinical characteristics, nonadherence, and outcomes between groups. High-risk patients were younger (48 vs. 56; p = 0.006) and more often on extracorporeal membrane oxygenation at durable MCS placement (26.9% vs. 9.0%; p = 0.007). These patients had a higher incidence of post-MCS nonadherence including missed clinic appointments, incorrect medication administration, and use of alcohol and illicit drugs. After a mean follow-up of 15.3 months, 100% of high-risk patients had unplanned hospitalizations compared with 76.8% of acceptable-risk patients. Per year, high-risk patients had a median of 2.9 hospitalizations per year vs. 1.2 hospitalizations per year in acceptable-risk patients. While not significant, there were more driveline infections over the follow-up period in high-risk patients (27% vs. 14.7%), deaths (27% vs. 18%), and fewer heart transplants (53.8% vs. 63.8%).The pre-MCS psychosocial assessment is associated with post-MCS evidence of nonadherence and unplanned hospitalizations. Attention to pre-MCS assessment of psychosocial risk factors is essential to optimize durable MCS outcomes.

Donor-specific antibodies in heart transplantation: can we afford the price or is it too steep to pay?

PURPOSE OF REVIEW: One-third of patients awaiting heart transplant are sensitized and 25-35% of heart allograft recipients develop de novo DSAs. Solid phase assays for DSA measurement have facilitated wider use of antibody monitoring and as such, our experience with DSAs is continuously evolving. RECENT FINDINGS: DSAs continue to exhibit poor correlation with biopsy-proven rejection. Novel molecular technologies, such as cell-free DNA and the molecular microscope (MMDx, which detects rejection-associated intragraft mRNA transcripts), are emerging as more sensitive methods to capture subclinical graft injury. High-resolution typing techniques are providing insight into the differential immunogenicity of HLA classes through epitope and eplet analysis. As sensitization of the transplant population is continuing to rise, our repertoire of desensitization strategies is also expanding. However, there is an acute need of predictive algorithms to help forecast the responders and the durability of desensitization. Novel immunomodulatory therapies have allowed safely transplanting across a positive crossmatch with good short-term survival but reported greater degree of rejection and lower long-term graft survival. SUMMARY: Our experience of outcomes as pertaining to DSAs still originates primarily from single-center studies. Our field is confronted with the challenge to establish common practice algorithms for the monitoring and treatment of DSAs.

Omission of Heart Transplant Recipients From the Appropriate Use Criteria for Revascularization and the Ramifications on Heart Transplant Centers.

Importance: Guidelines endorse routine coronary angiography and percutaneous coronary intervention (PCI) to screen for and treat cardiac allograft vasculopathy in heart transplant recipients. However, the current Appropriate Use Criteria for Revascularization (AUC-R) do not recognize prior heart transplant as a unique PCI indication. Whether this affects rates of rarely appropriate (RA) PCIs is unknown. Objective: To assess the rate of RA PCI procedures in heart transplant recipients and how it pertains to hospital PCI appropriateness metrics and pay-for-performance scorecards. Design, Setting, and Participants: This observational study used National Cardiovascular Data Registry CathPCI Registry data on all patients undergoing elective PCIs from 96 Medicare-approved heart transplant centers from quarter 3 of 2009 to quarter 2 of 2017. The data were analyzed in July 2018. Exposures: Prior heart transplant. Main Outcomes and Measures: Rates of RA elective PCIs in heart transplant recipients compared with nonrecipients and hospital rates of RA PCI before vs after exclusion of heart transplant recipients using paired t tests. In a subset of heart transplant centers participating in the Anthem Blue Cross and Blue Shield's Quality-In-Sights Hospital Incentive Program (Q-HIP), we compared the change in Q-HIP scorecards before vs after excluding heart transplant recipients. Results: Of 168 802 participants, 123 124 (72.9%) were men, 137 457 were white, and the mean (SD) age was 66.3 (11.4) years. Of 168 802 elective PCIs performed in heart transplant centers, 1854 (1.1%) were for heart transplant recipients. Heart transplant recipients were less likely to have ischemic symptoms (14.6% vs 61.4%, P < .001), had lower rates of antecedent stress testing (15.0% vs 58.4%, P < .001), and had higher RA PCI rates (66.0% vs 16.9%, P < .001) compared with nonrecipients. In heart transplant centers, the absolute difference in RA rates (before vs after excluding transplant recipients) was directly associated with the proportion of PCIs performed in heart transplant recipients (r = 0.91; P < .001). In the subset of heart transplant centers participating in Q-HIP during the 2016 and 2017 calendar years, 8 of 20 (40%) and 8 of 16 centers (50%), respectively, could have benefited from a change in their Q-HIP scorecards if their RA PCI rates excluded transplant recipients. Conclusions and Relevance: Two-thirds of PCIs in heart transplant recipients were deemed RA by the AUC-R. The failure of the AUC-R to consider prior heart transplant as a unique PCI indication may lead to inflated RA PCI rates with the potential for affecting quality reporting and pay-for-performance metrics in heart transplant centers.

Report from the American Society of Transplantation on frailty in solid organ transplantation.

A consensus conference on frailty in kidney, liver, heart, and lung transplantation sponsored by the American Society of Transplantation (AST) and endorsed by the American Society of Nephrology (ASN), the American Society of Transplant Surgeons (ASTS), and the Canadian Society of Transplantation (CST) took place on February 11, 2018 in Phoenix, Arizona. Input from the transplant community through scheduled conference calls enabled wide discussion of current concepts in frailty, exploration of best practices for frailty risk assessment of transplant candidates and for management after transplant, and development of ideas for future research. A current understanding of frailty was compiled by each of the solid organ groups and is presented in this paper. Frailty is a common entity in patients with end-stage organ disease who are awaiting organ transplantation, and affects mortality on the waitlist and in the posttransplant period. The optimal methods by which frailty should be measured in each organ group are yet to be determined, but studies are underway. Interventions to reverse frailty vary among organ groups and appear promising. This conference achieved its intent to highlight the importance of frailty in organ transplantation and to plant the seeds for further discussion and research in this field.

Sensitization in Transplantation: Assessment of Risk (STAR) 2017 Working Group Meeting Report.

The presence of preexisting (memory) or de novo donor-specific HLA antibodies (DSAs) is a known barrier to successful long-term organ transplantation. Yet, despite the fact that laboratory tools and our understanding of histocompatibility have advanced significantly in recent years, the criteria to define presence of a DSA and assign a level of risk for a given DSA vary markedly between centers. A collaborative effort between the American Society for Histocompatibility and Immunogenetics and the American Society of Transplantation provided the logistical support for generating a dedicated multidisciplinary working group, which included experts in histocompatibility as well as kidney, liver, heart, and lung transplantation. The goals were to perform a critical review of biologically driven, state-of-the-art, clinical diagnostics literature and to provide clinical practice recommendations based on expert assessment of quality and strength of evidence. The results of the Sensitization in Transplantation: Assessment of Risk (STAR) meeting are summarized here, providing recommendations on the definition and utilization of HLA diagnostic testing, and a framework for clinical assessment of risk for a memory or a primary alloimmune response. The definitions, recommendations, risk framework, and highlighted gaps in knowledge are intended to spur research that will inform the next STAR Working Group meeting in 2019.

Predicting 1-year cardiac transplantation survival using a donor-recipient risk-assessment tool.

OBJECTIVE: Many donor and recipient factors influence 1-year survival of patients after cardiac transplantation. To date, a statistical model has not been developed to assess the interplay of these factors in predicting outcomes, so we developed a risk-assessment tool to enhance decision-making. METHODS: We analyzed 29 variables that were reported in the United Network for Organ Sharing database for 24,540 cardiac transplantations performed between January 1, 2000, and June 30, 2015. For one half of the patients (the prediction population), a multivariable Cox regression model and the bootstrap resampling method were used to devise a scoring system predicting 1-year survival. The other half (the validation population) were stratified by score into 3 risk categories: high risk, medium risk, and low risk. One-year survival was compared among the 3 groups. RESULTS: Eleven variables were statistically significant in predicting 1-year survival. One-year survival for patients with risk scores of less than or equal to 8, 9 to 15, and greater than 15 were 91.2%, 81.7%, and 64.6%, respectively (P < .001). The C index of the Cox regression model was calculated at 0.62 when using risk score as a continuous predictor. CONCLUSIONS: Donor and recipient risk factors influence patient survival after cardiac transplantation. Long-term outcomes may be optimized with a statistically based risk model to improve donor-recipient matching.

Multidisciplinary approach to cardiac and pulmonary vascular disease risk assessment in liver transplantation: An evaluation of the evidence and consensus recommendations.

Liver transplant (LT) candidates today are older, have greater medical severity of illness, and have more cardiovascular comorbidities than ever before. In addition, there are specific cardiovascular responses in cirrhosis that can be detrimental to the LT candidate. Cirrhotic cardiomyopathy, a condition characterized by increased cardiac output and a reduced ventricular response to stress, is present in up to 30% of patients with cirrhosis, thus challenging perioperative management. Current noninvasive tests that assess for subclinical coronary and myocardial disease have low sensitivity, and altered hemodynamics during the LT surgery can unmask latent cardiovascular disease either intraoperatively or in the immediate postoperative period. Therefore, this review, assembled by a group of multidisciplinary experts in the field and endorsed by the American Society of Transplantation Liver and Intestine and Thoracic and Critical Care Communities of Practice, provides a critical assessment of the diagnosis of cardiac and pulmonary vascular disease and interventions aimed at managing these conditions in LT candidates. Key points and practice-based recommendations for the diagnosis and management of cardiac and pulmonary vascular disease in this population are provided to offer guidance for clinicians and identify gaps in knowledge for future investigations.

Proceedings of the AST heart allocation meeting at the American Transplant Congress, Philadelphia, Pennsylvania, May 4, 2015.

Ensuring fair and equitable allocation of donor hearts in the US is the charge of the Organ Procurement and Transplantation Network (OPTN). However, the recent increase of candidates waiting without a corresponding increase in available donors, higher waitlist mortality rates in higher status patients, the presence of disadvantaged subgroups, and the changing management of heart failure patients with increased VAD usage, has necessitated review of allocation policy. Therefore, the Heart Subcommittee of the OPTN/UNOS Thoracic Committee is exploring a further-tiered allocation system, devising a "straw man" model as a starting point for modeling analyses and public discussion. On May 4, 2015, an American Society of Transplantation (AST)-endorsed forum to discuss these potential proposed changes took place. Attendees included 41 people, mostly highly experienced transplant cardiologists and cardiothoracic surgeons, representing 19 heart transplant centers across the US, UNOS, and the Scientific Registry of Transplant Recipients (SRTR). There was unanimous agreement that the potential proposed policy will require careful wording to avoid ambiguity and "gaming" of the system, and strong support for abolishment of local organ sharing in favor of geographic sharing. However, contention existed concerning the appropriate prioritization levels of ECMO, temporary VAD/TAH patients as well as the 30-day LVAD listing.

Predictors of quality of life at 5 to 6 years after heart transplantation.

BACKGROUND: Only a few researchers have examined quality of life (QOL) outcomes more than 5 years after heart transplantation. Therefore, the purpose of this study was to describe QOL (overall, satisfaction with, and perceived importance); identify differences in QOL by age, sex, and race; and identify predictors of QOL at 5 to 6 years after heart transplantation. METHODS: A nonrandom sample of 231 patients (60 years of age, 76% men, 90% white, 79% married, and fairly well educated) who were 5 to 6 years after heart transplantation were investigated. Patients completed 12 QOL instruments via self-report. Data analyses included descriptive statistics, chi2, independent t-tests, correlations, and stepwise multiple regression. Level of significance was set at 0.05. RESULTS: Patient satisfaction with all areas of life was high at 5 to 6 years after heart transplantation. Similarly, patients believed that these same areas of life were very important. Yet areas of QOL with lower levels of satisfaction were identified. Patients who were > or =60 years were more satisfied with their QOL than patients <60 years. At 5 to 6 years after heart transplantation, almost 80% of variance in QOL was explained by psychological, physical, social, clinical, and demographic variables. CONCLUSIONS: At 5 to 6 years after heart transplantation, patients were very satisfied with their QOL, although differences in level of satisfaction were identified by demographic variables, and areas of QOL with lower levels of satisfaction were identified. Understanding those variables that contribute to QOL in the long term after heart transplantation provides direction for assisting patients to improve their QOL.

Physical activity patterns in heart transplant women.

Maintaining regular, long-term physical activity is critical to achieve favorable effects of heart transplantation. Yet, at present, little is known about the physical activity patterns of transplant recipients, especially women. The study was conducted to (1) describe levels and types of physical activity using actigraphy and self-report, (2) determine the association between physical activity and sociodemographic variables, and (3) assess the relationship between physical activity, quality of life (QOL), and relevant health indicators (hypertension, hyperlipidemia, and obesity) among female heart transplant recipients. Twenty-seven women (average age, 57 +/- 13 years, primarily Caucasian [82%], retired [89%], married [67%], average time since transplant 2.1 +/- 1.3 years) from a single heart transplant facility were asked to report amount and types of physical activity and overall QOL and wear an actigraph for 1 week to measure physical activity level. Physical activity levels by actigraphy averaged 280,320 +/- 52,416 counts for the week (range, 206,784-354,144); self-reported physical activity level on a 0 to 10 scale was 4.3 +/- 0.37 (range, 0-7). The actigraph and self-reported measures were significantly correlated (r = 0.661, P = .000). It was found that women were more likely to engage in household tasks and family activities than occupational activities or sports. Significant differences in physical activity (F = 6.319, P = .006) were observed in participants who reported fair (n = 13), good (n = 9), and very good (n = 5) overall QOL. The only demographic factor associated with physical activity was age; younger women were more active than older women (r = -0.472, P = .013). A negative correlation was found between levels of physical activity and presence of hypertension, hyperlipidemia, and obesity. It was found that a majority of female transplant recipients remains sedentary. Given the association between physical activity and overall QOL and relevant health indicators, measures to enhance physical activity need to be developed and tested; these strategies may be beneficial in improving overall outcomes.

The economic implications of noninvasive molecular testing for cardiac allograft rejection.

Endomyocardial biopsy is the mainstay for monitoring cardiac allograft rejection. A noninvasive strategy--peripheral blood gene expression profiling of circulating leukocytes--is an alternative with proven benefits, but unclear economic implications. Financial data were obtained from five cardiac transplant centers. An economic evaluation was conducted to compare the costs of outpatient biopsy with those of a noninvasive approach to monitoring cardiac allograft rejection. Hospital outpatient biopsy costs averaged 3297 US dollars, excluding reimbursement for professional fees. Costs to Medicare and private payers averaged 3581 US dollars and 4140 US dollars, respectively. A noninvasive monitoring test can reduce biopsy utilization. The savings to health care payers in the United States can be conservatively estimated at approximately 12.0 million US dollars annually. Molecular testing using gene expression profiling of peripheral circulating leukocytes is a new technology that offers physicians a noninvasive, less expensive alternative to endomyocardial biopsy for monitoring allograft rejection in cardiac transplant patients.