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

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.

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.

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.

During the study period, 860 adults and 84 children underwent HT. Among adults, the IRs (reported as cases per 100 person-years) of DM2, overweight or obesity, dyslipidemia, and CKD were 28.6, 77.3, 139.1, and 69.7, respectively. Among children, the IRs of DM2, overweight or obesity, dyslipidemia, and CKD were 2.8, 26.9, 5.5, and 3.6. Within 12 months post-HT, 99% of adults developed stage 1 or 2 hypertension, and 22.1% of all adults developed hemoglobin A_1c levels ≥6.5%, regardless of a preexisting diagnosis of DM2. Similarly, 37.5% of adults developed moderate to severe hypertriglyceridemia and 31.1% manifested worsened low-density lipoprotein cholesterol control. Among adults with an estimated glomerular filtration rate (eGFR) ≥45 mL/min/1.73 m² pre-HT, 86.2% displayed worsening renal function (eGFR <45 mL/min/1.73 m²) 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).

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.