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Graft Failure, Post-Transplant Adherence, and Access to Care in Emerging Adult Heart Transplantation
Sara Sakowitz1, Syed Shahyan Bakhtiyar2, Yas Sanaiha3, Richard Shemin3, Peyman Benharash3
1Surgery, Massachusetts General Hospital, Boston, MA, 2Cardiac Surgery, University of Utah Health, Salt Lake City, UT, 3Cardiac Surgery, University of California Los Angeles David Geffen School of Medicine, Los Angeles, CA
OBJECTIVE
Heart transplantation (HT) remains a life-saving treatment for cardiac failure, but its impact remains limited by long-term graft durability. Emerging adulthood (ages 17-25), a vulnerable developmental stage marked by new autonomy, shifting roles, and changes in healthcare coverage, has been identified as a high-risk interval for graft loss in renal transplantation. Whether a similar high-risk interval exists among emerging adult HT recipients, and the extent to which structural factors, such as insurance coverage or access to care contribute to this risk, has yet to be comprehensively elucidated. We sought to characterize age-specific graft failure risk following HT and to examine the roles of Medicaid insurance and post-transplant non-adherence in shaping outcomes among emerging adult recipients.
METHODS
This study tabulated all transplant-naïve, adult isolated HT recipients from 2005-2025 from the Scientific Registry of Transplant Recipients. Emerging adulthood was defined as recipient age 17-29 years. Kaplan-Meier and time-adjusted Cox proportional hazard models evaluated the association of emerging adulthood with graft failure risk and non-adherence to post-transplant therapy. Covariates were automatically selected and included sex, race/ethnicity, insurance status, body mass index, comorbidities, transplant indication, and allograft ischemia time, as well as donor age, sex, race, history of diabetes/hypertension, and recipient-donor cytomegalovirus (CMV) status. To assess mechanistic pathways, we conducted a causal mediation analysis to assess whether Medicaid insurance mediated the relationship between emerging adulthood and graft failure.
The primary outcome of interest was graft failure over five years following HT. We secondarily considered non-adherence in the post-transplant period.
RESULTS
In total, we identified 43,739 HT recipients ≥30 years (92%) and 3,584 emerging adult recipients (8%, 17-29 years). On average, emerging adult recipients were more commonly female, of Black race and Medicaid insurance, and more often transplanted for dilated cardiomyopathy (Table).
At five years, 14% of the emerging adult cohort had developed graft failure, compared to 6% of all other adult recipients. Following comprehensive risk-adjustment, emerging adulthood remained associated with a two-fold increase in the relative risk of graft failure (HR 2.03, CI 1.78-2.31, FigA). This persisted across age strata, such that emerging adults demonstrated greater graft failure risk relative to those 30-39 years (HR 1.56, CI 1.32-1.84), 40-49 years (HR 1.74, CI 1.49-2.03), and ≥50 years (HR 2.31, CI 2.02-2.65) (FigB).
Several other factors were found to be linked with graft failure risk, including Medicaid insurance (HR 1.38, CI 1.24-1.54) and Black race (HR 1.63, CI 1.48-1.79). After risk-adjustment, emerging adults with Medicaid insurance demonstrated a nearly three-fold increase in graft failure risk, compared to non-Medicaid insured others (HR 2.98, CI 2.50-3.57; FigC). Mediation analysis revealed that Medicaid insurance mediated 8.7% of the association between emerging adulthood and graft failure following HT (CI 7.0-10.9%).
Notably, 21% of emerging adults demonstrated non-adherence, compared to 6% of others. After adjustment, emerging adults with documented non-compliance faced a ~7 fold higher risk of graft failure, relative to older, adherent HT recipients (FigD).
CONCLUSIONS
Emerging adulthood represents a distinct and clinically consequential, high-risk period following HT, characterized by both disproportionately high graft failure and non-adherence rates. While Medicaid insurance partially mediates this vulnerability, most excess risk stems from factors beyond insurance alone. Our findings highlight this group as a priority group for targeted, age-specific interventions, including structured transition-of-care programs and policies aimed at stabilizing insurance coverage, to improve long-term graft durability and survival.
FIGURE: Kaplan-Meier time-to-event analyses of allograft failure following heart transplantation. (A) Emerging adult recipients (17-24 years) demonstrated inferior allograft survival over 5 years following transplantation, compared to other adults ≥30 years. (B) Emerging adults demonstrated distinct, and inferior, allograft survival patterns from recipients 30-39 years, 40-49 years, and ≥50 years. (C) We noted an interaction between emerging adult status and Medicaid insurance, such that Medicaid insurance mediated approximately 9% of the relationship between emerging adult status and graft outcomes. (D) Finally, examining adherence to treatment in the years following heart transplantation, we found 21% of emerging adults to demonstrate treatment non-compliance, compared with adults ≥30 years. Emerging adults who were non-compliant with treatment demonstrated dramatically reduced allograft survival, compared to all others.
Table 1: Heart Transplant Recipient and Donor Characteristics, Stratified by Emerging Heart Transplant Recipient Status. Patients aged 17-29 were considered the emerging HT cohort. All values as reported by the Scientific Registry of Transplant Recipients. *BMI, Body Mass Index; IQR: Interquartile Range; SD: Standard Deviation; AAPI, Asian American and Pacific Islander
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