Residential Environmental Composition and Risk of Acute Cellular Rejection After Heart Transplantation: A Multi-Scale...

Background: Acute cellular rejection (ACR) after heart transplantation remains incompletely explained despite standardized immunosuppression. Environmental exposures may contribute to residual immune activation; however, prior studies have focused primarily on air pollution rather than residential land-use composition. Objectives: To determine whether buffer-specific residential environmental composition is associated with rejection risk and whether these associations are scale-dependent and domain-specific. Methods: In this retrospective single-center cohort study, 30 heart transplant recipients contributed 267 biopsy-linked observations. Residential land-use composition was quantified within 300 m, 500 m, 700 m, and 1000 m buffers and aggregated into five domains: trees, other green surroundings, roads, water, and industrial land. Associations with ACR were evaluated using clustered logistic regression models adjusted for time since transplantation. Results: The strongest and only statistically robust associations after FDR correction were observed within the 300 m buffer. Tree-dominant (OR 1.42, 95% CI 1.22-1.65, q = 0.010) and industrial land exposure (OR 1.50, 95% CI 1.28-1.76, q = 0.010) were independently associated with increased odds of ACR. At 500 m, the association with trees persisted nominally (OR 1.39, 95% CI 1.03-1.88, p = 0.034), but did not remain significant after FDR correction, whereas water exposure showed a non-significant trend (OR 1.28, p = 0.057), which did not reach statistical significance. No associations were observed beyond 700 m across all models. Conclusions: Residential environmental composition may be associated with acute cellular rejection after heart transplantation in a scale-dependent manner, with signals confined to the immediate residential environment. Tree-dominant exposure within 300 m showed an association in clustered models; however, this finding was attenuated in mixed-effects sensitivity analyses. These results should be considered exploratory and hypothesis-generating study.