SCARF1-Induced Efferocytosis Plays an Immunomodulatory Role in Humans, and Autoantibodies Targeting SCARF1 Are Produced in Patients with Systemic Lupus Erythematosus.

Deficiency in the clearance of cellular debris is a major pathogenic factor in the emergence of autoimmune diseases. We previously demonstrated that mice deficient for scavenger receptor class F member 1 (SCARF1) develop a lupus-like autoimmune disease with symptoms similar to human systemic lupus erythematosus (SLE), including a pronounced accumulation of apoptotic cells (ACs). Therefore, we hypothesized that SCARF1 will be important for clearance of ACs and maintenance of self-tolerance in humans, and that dysregulation of this process could contribute to SLE. In this article, we show that SCARF1 is highly expressed on phagocytic cells, where it functions as an efferocytosis receptor. In healthy individuals, we discovered that engagement of SCARF1 by ACs on BDCA1+ dendritic cells initiates an IL-10 anti-inflammatory response mediated by the phosphorylation of STAT1 and STAT3. Unexpectedly, there was no significant difference in SCARF1 expression in samples of patients with SLE compared with healthy donor samples. However, we detected anti-SCARF1 autoantibodies in 26% of patients with SLE, which was associated with dsDNA Ab positivity. Furthermore, our data show a direct correlation of the levels of anti-SCARF1 in the serum and defects in the removal of ACs. Depletion of Ig restores efferocytosis in SLE serum, suggesting that defects in the removal of ACs are partially mediated by SCARF1 pathogenic autoantibodies. Our data demonstrate that human SCARF1 is an AC receptor in dendritic cells and plays a role in maintaining tolerance and homeostasis.

Hydroxychloroquine Dose and Risk for Incident Retinopathy : A Cohort Study.

BACKGROUND: Hydroxychloroquine is recommended for all patients with systemic lupus erythematosus and is often used for other inflammatory conditions, but a critical long-term adverse effect is vision-threatening retinopathy. OBJECTIVE: To characterize the long-term risk for incident hydroxychloroquine retinopathy and examine the degree to which average hydroxychloroquine dose within the first 5 years of treatment predicts this risk. DESIGN: Cohort study. SETTING: U.S. integrated health network. PARTICIPANTS: All patients aged 18 years or older who received hydroxychloroquine for 5 or more years between 2004 and 2020 and had guideline-recommended serial retinopathy screening. MEASUREMENTS: Hydroxychloroquine dose was assessed from pharmacy dispensing records. Incident hydroxychloroquine retinopathy was assessed by central adjudication of spectral domain optical coherence tomography with severity assessment (mild, moderate, or severe). Risk for hydroxychloroquine retinopathy was estimated over 15 years of use according to hydroxychloroquine weight-based dose (>6, 5 to 6, or ≤5 mg/kg per day) using the Kaplan-Meier estimator. RESULTS: Among 3325 patients in the primary study population, 81 developed hydroxychloroquine retinopathy (56 mild, 17 moderate, and 8 severe), with overall cumulative incidences of 2.5% and 8.6% at 10 and 15 years, respectively. The cumulative incidences of retinopathy at 15 years were 21.6% for higher than 6 mg/kg per day, 11.4% for 5 to 6 mg/kg per day, and 2.7% for 5 mg/kg per day or lower. The corresponding risks for moderate to severe retinopathy at 15 years were 5.9%, 2.4%, and 1.1%, respectively. LIMITATION: Possible misclassifications of dose due to nonadherence to filled prescriptions. CONCLUSION: In this large, contemporary cohort with active surveillance retinopathy screening, the overall risk for hydroxychloroquine retinopathy was 8.6% after 15 years, and most cases were mild. Higher hydroxychloroquine dose was associated with progressively greater risk for incident retinopathy. PRIMARY FUNDING SOURCE: National Institutes of Health.

Exploration of machine learning methods to predict systemic lupus erythematosus hospitalizations.

OBJECTIVES: Systemic lupus erythematosus (SLE) is a heterogeneous disease characterized by disease flares which can require hospitalization. Our objective was to apply machine learning methods to predict hospitalizations for SLE from electronic health record (EHR) data. METHODS: We identified patients with SLE in a longitudinal EHR-based cohort with ≥2 outpatient rheumatology visits between 2012 and 2019. We applied multiple machine learning methods to predict hospitalizations with a primary diagnosis code for SLE, including decision tree, random forest, naive Bayes, logistic regression, and an ensemble method. Candidate predictors were derived from structured EHR features, including demographics, laboratory tests, medications, ICD-9/10 codes for SLE manifestations, and healthcare utilization. We used two approaches to assess these variables over longitudinal follow-up, including the incorporation of lagged features to capture changes over time of clinical data. The performance of each model was evaluated by overall accuracy, the F statistic, and the area under the receiver operator curve (AUC). RESULTS: We identified 1996 patients with SLE. 4.6% were hospitalized for SLE in their most recent year of follow-up. Random forest models had highest performance in predicting SLE hospitalizations, with AUC 0.751 and AUC 0.772 for two approaches (averaging and progressive), respectively. The leading predictors of SLE hospitalizations included dsDNA positivity, C3 level, blood cell counts, and inflammatory markers as well as age and albumin. CONCLUSION: We have demonstrated that machine learning methods can predict SLE hospitalizations. We identified key predictors of these events including known markers of SLE disease activity; further validation in external cohorts is warranted.

Coronavirus disease 2019 outcomes among patients with rheumatic diseases 6 months into the pandemic.

OBJECTIVE: In earlier studies, patients with rheumatic and musculoskeletal disease (RMD) who got infected with COVID-19 had a higher risk of mechanical ventilation than comparators. We sought to determine COVID-19 outcomes among patients with RMD 6 months into the pandemic. METHODS: We conducted a cohort study at Mass General Brigham in Boston, Massachusetts, of patients with RMD matched to up to five comparators by age, sex and COVID-19 diagnosis date (between 30 January 2020 and 16 July 2020) and followed until last encounter or 18 August 2020. COVID-19 outcomes were compared using Cox regression. Risk of mechanical ventilation was compared in an early versus a recent cohort of patients with RMD. RESULTS: We identified 143 patients with RMD and with COVID-19 (mean age 60 years; 76% female individuals) and 688 comparators (mean age 59 years; 76% female individuals). There were no significantly higher adjusted risks of hospitalisation (HR: 0.87, 95% CI: 0.68-1.11), intensive care unit admission (HR: 1.27, 95% CI: 0.86-1.86), or mortality (HR: 1.02, 95% CI: 0.53-1.95) in patients with RMD versus comparators. There was a trend towards a higher risk of mechanical ventilation in the RMD cohort versus comparators, although not statistically significant (adjusted HR: 1.51, 95% CI: 0.93-2.44). There was a trend towards improvement in mechanical ventilation risk in the recent versus early RMD cohort (10% vs 19%, adjusted HR: 0.44, 95% CI: 0.17-1.12). CONCLUSIONS: Patients with RMD and comparators had similar risks of poor COVID-19 outcomes after adjusting for race, smoking and comorbidities. The higher risk of mechanical ventilation in the early RMD cohort was no longer detected in a recent cohort, suggesting improved management over time.

Comparison of an administrative algorithm for SLE disease severity to clinical SLE Disease Activity Index scores.

Systemic lupus erythematosus (SLE) severity, reflecting both disease intensity and duration, is heterogeneous making it challenging to study in administrative databases where severity may confound or mediate associations with outcomes. Garris et al. developed an administrative claims-based algorithm employing claims over a 1-year period to classify SLE severity as mild, moderate or severe. We sought to compare this administrative algorithm to a measure of SLE activity, the SLE Disease Activity Index-2000 (SLEDAI-2K) score at clinical visits. We identified 100 SLE patients followed in the Brigham and Women's Hospital (BWH) Lupus Center (in 2008-2010) with SLEDAI-2K scores at each visit over a 1-year period per person. We obtained data for the Garris algorithm for the same year per subject. We compared Garris SLE severity to the highest SLEDAI-2K in that year, with SLEDAI-2K categories of mild < 3, moderate 3-6, and severe > 6. We compared classification using weighted kappa statistics, and positive and negative predictive values (PPV, NPV). We also assessed the binary comparison of mild vs. moderate/severe. We calculated sensitivity, specificity, and McNemar's test. We analyzed 377 SLEDAI-2K assessments (mean 3.8 [SD 2.6] per subject/year). For classifying moderate/severe vs. mild SLE severity, the sensitivity was 85.7%, specificity 67.6%, PPV 81.8% and NPV 73.5%. The Garris algorithm for classifying SLE severity in administrative datasets had moderate agreement for classification of mild vs. moderate/severe SLE activity assessed by SLEDAI-2K assessments in an academic lupus center. It may be a useful tool for classifying SLE severity in administrative database studies.

Renal Transplantation and Survival Among Patients With Lupus Nephritis: A Cohort Study.

Background: Patients with end-stage renal disease (ESRD) due to lupus nephritis (LN) have high rates of premature death. Objective: To assess the potential effect on survival of renal transplant among patients with ESRD due to LN (LN-ESRD) in the United States. Design: Nationwide cohort study. Setting: United States Renal Data System, the national database of nearly all patients with ESRD. Participants: Patients with incident LN-ESRD who were waitlisted for a renal transplant. Measurements: First renal transplant was analyzed as a time-varying exposure. The primary outcomes were all-cause and cause-specific mortality. Time-dependent Cox regression analysis was used to estimate the hazard ratio (HR) of these outcomes associated with renal transplant in the primary analysis. Sequential cohort matching was used in a secondary analysis limited to patients with Medicare, which allowed assessment of time-varying covariates. Results: During the study period, 9659 patients with LN-ESRD were waitlisted for a renal transplant, of whom 5738 (59%) had a transplant. Most were female (82%) and nonwhite (60%). Transplant was associated with reduced all-cause mortality (adjusted HR, 0.30 [95% CI, 0.27 to 0.33]) among waitlisted patients. Adjusted HRs for cause-specific mortality were 0.26 (CI, 0.23 to 0.30) for cardiovascular disease, 0.30 (CI, 0.19 to 0.48) for coronary heart disease, 0.41 (CI, 0.32 to 0.52) for infection, and 0.41 (CI, 0.31 to 0.53) for sepsis. Limitation: Unmeasured factors may contribute to the observed associations; however, the E-value analysis suggested robustness of the results. Conclusion: Renal transplant was associated with a survival benefit, primarily due to reduced deaths from cardiovascular disease and infection. The findings highlight the benefit of timely referral for transplant to improve outcomes in this population. Primary Funding Source: National Institutes of Health.

Unchanging premature mortality trends in systemic lupus erythematosus: a general population-based study (1999-2014).

Objective: Patients with SLE have increased morbidity and premature mortality. Whether this mortality gap has improved in recent years, as in RA, is unknown. Methods: We conducted a population-based cohort study using a medical records database representative of the general population of the UK. We identified incident SLE cases and matched non-SLE controls between 1999 and 2014, divided into two subgroups based on year of SLE diagnosis, forming the early cohort (1999-2006) and late cohort (2007-14). We compared the mortality rates and hazard ratios, adjusting for potential confounders. Results: We identified 1470 and 1666 incident SLE cases in the early and late cohorts, respectively. In both cohorts, SLE patients had similar levels of excess mortality compared with their matched comparators [15.9 vs 7.9 deaths/1000 person-years (PY) in the early cohort and 13.8 vs 7.0 deaths/1000 PY in the late cohort]. The corresponding mortality hazard ratios were 2.15 (95% CI 1.63, 2.83) and 2.12 (95% CI 1.61, 2.80) in the early and late cohorts, respectively (P-value for interaction = 0.95). The absolute mortality differences were 8.0 (95% CI 4.3, 11.8) and 6.8 (95% CI 3.5, 10.0) deaths/1000 PY, respectively (P-value for interaction = 0.61). Conclusion: This general population-based cohort study suggests that excess mortality has not improved among SLE patients in recent years, remaining greater than double that of comparators, unlike RA during the same period. This highlights a critical unmet need for the development of new therapeutic agents and improved management strategies for SLE and its comorbidities.

Hydroxychloroquine Dose per Ophthalmology Guidelines and the Risk of Systemic Lupus Erythematosus Flares.

This study of an academic medical center patient cohort with systemic lupus erythematosus (SLE) investigates the association between hydroxychloroquine dose based on current guidelines and risk of lupus flares.

Hydroxychloroquine Dose and Hospitalizations for Active Lupus.

OBJECTIVE: We sought to determine the impact of hydroxychloroquine (HCQ) dose on the risk of hospitalizations for systemic lupus erythematosus (SLE). METHODS: We conducted a case-crossover study within an academic health system, including patients with SLE who used HCQ and had ≥1 hospitalization for active SLE between January 2011 and December 2021. Case periods ended in hospitalization for SLE, whereas control periods did not. The exposures were the average weight-based HCQ dose, categorized as ≤5 or >5 mg/kg/day, and non-weight-based HCQ dose, categorized as <400 or 400 mg/day, assessed during each six-month case or control period. Odds ratios (ORs) were calculated using conditional logistic regression and adjusted for prior disease activity, kidney function, glucocorticoid use, and other immunosuppressant use. RESULTS: Of 2,974 patients with SLE who used HCQ (mean age 36.5 years; 92% female), 584 had ≥1 hospitalization with primary discharge diagnosis of SLE. Of these, 122 had ≥1 hospitalization for active SLE while using HCQ and had ≥1 control period with HCQ use during the study period. Lower HCQ weight-based dose (≤5 vs >5 mg/kg/day) and non-weight-based dose (<400 vs 400 mg/day) were each associated with increased hospitalizations for active SLE (adjusted OR 4.20, 95% confidence interval [CI] 1.45-12.19, and adjusted OR 3.39, 95% CI 1.31-8.81). CONCLUSION: The use of lower doses of HCQ was associated with an increased risk of hospitalizations for active SLE. Although the long-term risk of HCQ retinopathy must be acknowledged, this must be balanced with the short-term and cumulative risks of increased SLE activity.

Risk Factors for Hydroxychloroquine Retinopathy and Its Subtypes.

Importance: The major toxic effect of hydroxychloroquine is retinopathy. Thus, current guidelines recommend limiting the dose and screening annually for retinopathy among all long-term users, but individual patient factors may be associated with retinopathy risk. Objective: To identify risk factors beyond hydroxychloroquine dose and duration of use for hydroxychloroquine retinopathy. Design, Setting, and Participants: This cohort study of 4677 patients in the Kaiser Permanente Northern California integrated health network who initiated hydroxychloroquine, continued treatment, and underwent retinopathy screening after 5 years of use was conducted from July 1, 1997, to December 31, 2020, with up to 15 years of follow-up. Statistical analysis was performed in August 2023. Exposure: Candidate risk factors included age at hydroxychloroquine initiation, sex, race and ethnicity, indications, chronic kidney disease (CKD), liver disease, diabetes, tamoxifen use, and medications that interact with hydroxychloroquine metabolism. Hydroxychloroquine dose was assessed from pharmacy dispensing records. Main Outcome and Measures: Incident hydroxychloroquine retinopathy was adjudicated from masked review of guideline-recommended screening studies and classified as parafoveal or pericentral pattern. Multivariable Cox proportional hazards regression was used to assess potential risk factors for hydroxychloroquine retinopathy within 15 years of initiation. Results: Of 4677 long-term hydroxychloroquine users (mean [SD] age at initiation, 52.4 [14.1] years; 3877 women [82.9%]), 125 patients developed hydroxychloroquine retinopathy within 15 years (102 parafoveal, 23 pericentral). Older age at time of hydroxychloroquine initiation was associated with retinopathy risk, with adjusted hazard ratios (HRs) of 2.48 (95% CI, 1.28-4.78) for those aged 45 to 54 years, 3.82 (95% CI, 2.05-7.14) for those aged 55 to 64 years, and 5.68 (95% CI, 2.99-10.79) for those aged 65 years or older compared with those younger than 45 years. The risk of retinopathy was higher among females than males (HR, 3.83 [95% CI, 1.86-7.89]), among patients with CKD stage 3 or greater (HR, 1.95 [95% CI, 1.25-3.04]), and among individuals with tamoxifen use (HR, 3.43 [95% CI, 1.08-10.89]). The likelihood of pericentral retinopathy was higher among Asian patients (HR, 15.02 [95% CI, 4.82-46.87]) and Black patients (HR, 5.51 [95% CI, 1.22-24.97]) compared with non-Hispanic White patients. Conclusions and Relevance: This study suggests that increasing age, female sex, CKD stage 3 or greater, and tamoxifen use were associated with a higher risk of hydroxychloroquine retinopathy, whereas being younger than 45 years at hydroxychloroquine initiation and male sex were associated with a lower risk. Race and ethnicity were also associated with the pattern of retinopathy. These factors should be incorporated into hydroxychloroquine dosing decisions.

Hydroxychloroquine Use and Cardiovascular Events Among Patients With Systemic Lupus Erythematosus and Rheumatoid Arthritis.

OBJECTIVE: We evaluated the potential temporal association between hydroxychloroquine (HCQ) use and cardiovascular (CV) events among patients with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA). METHODS: We conducted a nested case-control study within inception cohorts of SLE and RA patients using administrative health databases including the entire population of British Columbia, Canada. We identified cases with incident CV events, including myocardial infarction (MI), stroke, or venous thromboembolism (VTE). We matched each case with up to 3 controls on age, sex, and rheumatic disease. HCQ exposure was categorized by the time between the last HCQ prescription date covered and the index date as current use, recent use, remote use, or never used. We used conditional logistic regression to assess the association between HCQ exposure and CV events, using remote use as the reference group. RESULTS: We identified 10,268 cases and 29,969 controls. Adjusted conditional odd ratios (cORs) and 95% confidence intervals (95% CIs) for current HCQ use relative to remote use were 0.86 (0.77-0.97) for combined CV events, 0.88 (0.74-1.05) for MI, 0.87 (0.74-1.03) for stroke, and 0.74 (0.59-0.94) for VTE. Recent HCQ users and nonusers had similar odds of combined CV events as remote users (cORs 0.93, 95% CI 0.77-1.13 and 0.96, 95% CI 0.88-1.04, respectively). CONCLUSION: In this nested case-control study of patients with SLE and RA, we found a reduced risk of overall CV events associated with current HCQ use, including reductions in VTE and trends toward reductions in MI and stroke. These findings suggest a possible cardiovascular preventative benefit of HCQ use.

Comparative Risks of Infection With Belimumab Versus Oral Immunosuppressants in Patients With Nonrenal Systemic Lupus Erythematosus.

OBJECTIVE: We investigated the comparative risk of infection with belimumab versus oral immunosuppressants for the treatment of systemic lupus erythematosus (SLE). METHODS: Using observational data from a US multicenter electronic health record database, we identified patients with SLE but without lupus nephritis who initiated belimumab, azathioprine, methotrexate, or mycophenolate between 2011 and 2021. We designed and emulated hypothetical target trials to estimate the cumulative incidence and hazard ratios (HRs) of serious infection and hospitalization for serious infection comparing belimumab versus each oral immunosuppressant. We used propensity score overlap weighting to balance baseline covariates and adjusted for adherence to treatment group using inverse probability of treatment weighting. We also assessed the control outcome of traumatic injury. RESULTS: Among 21,481 patients, we compared 2841 and 6343 initiators of belimumab and azathioprine, 2642 and 8242 initiators of belimumab and methotrexate, and 2813 and 8407 initiators of belimumab and mycophenolate, respectively. After propensity score overlap weighting, all covariates were balanced in each comparison. The mean age of the cohort was 45 years, and 94% were women. Compared with azathioprine and mycophenolate, belimumab was associated with lower risks of both serious infection (HR 0.82; 95% confidence interval [CI] 0.72-0.92 and HR 0.69; 95% CI 0.61-0.78) and hospitalization for infection (HR 0.73; 95% CI 0.57-0.94 and HR 0.56 95% CI 0.43-0.71). The risk of infection was also lower for belimumab compared with methotrexate (HR 0.86; 95% CI 0.76-0.97). There were no differences in traumatic injury risks across treatment groups. CONCLUSION: Belimumab was associated with lower risks of serious infection than with oral immunosuppressants. This finding should inform risk/benefit considerations for SLE treatment.

Development of American College of Rheumatology Quality Measures for Systemic Lupus Erythematosus: A Modified Delphi Process With Rheumatology Informatics System for Effectiveness (RISE) Registry Data Review.

OBJECTIVE: We aimed to develop readily measurable digital quality measure statements for clinical care in systemic lupus erythematosus (SLE) using a multistep process guided by consensus methods. METHODS: Using a modified Delphi process, an American College of Rheumatology (ACR) workgroup of SLE experts reviewed all North American and European guidelines from 2000 to 2020 on treatment, monitoring, and phenotyping of patients with lupus. Workgroup members extracted quality constructs from guidelines, rated these by importance and feasibility, and generated evidence-based quality measure statements. The ACR Rheumatology Informatics System for Effectiveness (RISE) Registry was queried for measurement data availability. In 3 consecutive Delphi sessions, a multidisciplinary Delphi panel voted on the importance and feasibility of each statement. Proposed measures with consensus on feasibility and importance were ranked to identify the top 3 measures. RESULTS: Review of guidelines and distillation of 57 quality constructs resulted in 15 quality measure statements. Among these, 5 met high consensus for importance and feasibility, including 2 on treatment and 3 on laboratory monitoring measures. The 3 highest-ranked statements were recommended for further measure specification as SLE digital quality measures: 1) hydroxychloroquine use, 2) limiting glucocorticoid use >7.5 mg/day to <6 months, and 3) end-organ monitoring of kidney function and urine protein excretion at least every 6 months. CONCLUSION: The Delphi process selected 3 quality measures for SLE care on hydroxychloroquine, glucocorticoid reduction, and kidney monitoring. Next, measures will undergo specification and validity testing in RISE and US rheumatology practices as the foundation for national implementation and use in quality improvement programs.

Comparing two machine learning approaches in predicting lupus hospitalization using longitudinal data.

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease characterized by flares ranging from mild to life-threatening. Severe flares and complications can require hospitalizations, which account for most of the direct costs of SLE care. This study investigates two machine learning approaches in predicting SLE hospitalizations using longitudinal data from 925 patients enrolled in a multicenter electronic health record (EHR)-based lupus cohort. Our first Differential approach accounts for the time dependencies in sequential data by introducing additional lagged variables between consecutive time steps. We next evaluate the performance of LSTM, a state-of-the-art deep learning model designed for time series. Our experimental results demonstrate that both methods can effectively predict lupus hospitalizations, but each has its strengths and limitations. Specifically, the Differential approach can be integrated into any non-temporal machine learning algorithms and is preferred for tasks with short observation periods. On the contrary, the LSTM model is desirable for studies utilizing long observation intervals attributing to its capability in capturing long-term dependencies embedded in the longitudinal data. Furthermore, the Differential approach has more options in handling class imbalance in the underlying data and delivers stable performance across different prognostic horizons. LSTM, on the other hand, demands more class-balanced training data and outperforms the Differential approach when there are sufficient positive samples facilitating model training. Capitalizing on our experimental results, we further study the optimal length of patient monitoring periods for different prediction horizons.

Kidney Transplantation and Cardiovascular Events Among Patients With End-Stage Renal Disease Due to Lupus Nephritis: A Nationwide Cohort Study.

OBJECTIVE: To assess the potential impact of kidney transplantation on cardiovascular (CV) events among patients with end-stage renal disease (ESRD) due to lupus nephritis (LN). METHODS: In a nationwide cohort study, we identified all patients with LN-ESRD enrolled in the US Renal Data System who were waitlisted for a kidney transplant and enrolled in Medicare between January, 2000 and December, 2016. The primary outcome was incident CV events, including myocardial infarction (MI) and ischemic cerebrovascular accident (CVA). We used time-dependent Cox regression to estimate the hazard ratios (HRs) of these outcomes associated with kidney transplant as a time-varying exposure, adjusting for sex, age, race, ethnicity, geographic region, year of ESRD onset, first ESRD treatment modality (e.g., hemodialysis or peritoneal dialysis), Charlson Comorbidity Index score, and history of prior organ transplants. RESULTS: Of 5,963 waitlisted patients with LN-ESRD, 3,209 (54%) had a kidney transplant during the study period. The majority were female (82%), and African American patients represented 48% of waitlisted patients and 43% of transplanted patients. Kidney transplantation was associated with a lower risk of incident CV events (adjusted HR 0.31 [95% confidence interval (95% CI) 0.18-0.53]) as well as lower risks of MI and CVA (adjusted HRs 0.13 [95% CI 0.08-0.34] and 0.30 [95% CI 0.16-0.54], respectively). CONCLUSION: Kidney transplantation was associated with a reduced risk of CV events, including MI and CVA, in patients with LN-ESRD. Our findings highlight the importance of identifying barriers to transplantation in this population, as improved access could reduce CV morbidity.