October 21, 2025JACC Heart Failure6 citationsOpen Access

Cardiovascular-Kidney-Metabolic Disease Burden in Children and Adults Following Heart Transplantation

SHShi Huang JTJaclyn Tamaroff EFEric Farber‐Eger

Structured PICO

What is the incidence of cardiovascular-kidney-metabolic dysfunction following heart transplantation, and is it associated with adverse clinical outcomes?

Population

944 patients (860 adults and 84 children aged ≥2 years) who underwent heart transplantation between January 1, 2015, and June 30, 2024. Adult cohort: mean age 52.9 years, 30.1% female. Pediatric cohort: mean age 10.0 years, 44% female. Excluded: individuals referred by the Veterans Affairs system, and for eGFR analyses, those with simultaneous multiorgan transplantation or history of pre-HT dialysis.

Intervention

Post-heart transplantation standard care (observational cohort). A subset analysis evaluated the impact of initiating sodium-glucose cotransporter 2 (SGLT2) inhibitors (n=242) and glucagon-like peptide-1 receptor agonists (GLP1RAs) (n=168) post-transplant.

Outcome

Incidence and prevalence of cardiovascular-kidney-metabolic (CKM) risk factors (type 2 diabetes mellitus, overweight or obesity, hypertension, chronic kidney disease, and dyslipidemia) up to 36 months post-HT, and their association with cardiac allograft vasculopathy (CAV) and mortality.surrogate

Abstract

BACKGROUND: Heart transplantation (HT) is the definitive therapy for end-stage heart failure. However, with improving post-HT survival in the modern era, recipients are increasingly cumulatively exposed to unique risk factors for cardiovascular-kidney-metabolic (CKM) dysfunction. An expanded understanding of the incidence and prevalence of CKM dysfunction post-HT may inform screening and therapeutic strategies to mitigate adverse events. OBJECTIVES: The aim of this study was to characterize the incidence and prevalence of CKM risk factors in adult and pediatric HT recipients and to define their association with cardiac allograft vasculopathy (CAV) and mortality. METHODS: A single-center retrospective observational study was conducted in adults and children who underwent HT between January 1, 2015, and June 30, 2024. Longitudinal clinical and laboratory data were extracted from the electronic health record. Incidence rates (IRs) of type 2 diabetes mellitus (DM2), overweight or obesity, hypertension, chronic kidney disease (CKD), and dyslipidemia were calculated. longitudinal trajectories of CKM dysfunction were constructed, and the impact of sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP1RAs) on CKD and body mass index, respectively, was evaluated. Finally, immunologic and CKM comorbidities were linked with clinical outcomes by using time-varying Cox regression models. RESULTS: ) within 12 months post-HT. In adults initiated on SGLT2 inhibitor post-HT (n = 242), there was a nonlinear improvement in eGFR during the ensuing 12 months; for individuals initiated on GLP1RAs (n = 168), there was a predominantly linear reduction in body mass index. Among CKM comorbidities, none was significantly associated with CAV, whereas DM2 was associated with increased post-HT mortality (HR: 1.84; 95% CI: 1.04-3.25). CONCLUSIONS: A significant proportion of HT recipients experience new-onset or worsening CKM dysfunction after HT. Furthermore, CKM comorbidities are associated with post-HT mortality. These results indicate that SGLT2 inhibitors and GLP1RAs may mitigate the burden of CKM disease.

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