Arteriovenous fistula-induced cardiac remodeling shows cardioprotective features in mice

factors (Cdkn1a, FoxO3, a-catenin). The predicted downstream effects include a decrease in heart damage, and increased arrhythmia, angiogenesis, and cardiogenesis. There were no significant sex-dependent differences in the AVF-stimulated cardiac adaptation. Conclusions: AVF stimulate adaptive cardiac hypertrophy in wild-type mice without heart failure or pathologic fibrosis. Transcriptional correlates suggest AVF-induced cardiac remodeling has some cardioprotective, although also arrhyth- mogenic features. (JVSeVascular Science 2021;-:1-19.) Clinical Relevance: Arteriovenous fistulae (AVF) are commonly used as access for hemodialysis in patients with end-stage renal disease. AVFinduce a high-output state that is associated with long-term structural cardiac remodeling, including left ventricle hypertrophy, but this element has uncertain clinical significance. Although left ventricle hypertrophy has tradi- tionally been associated with an increased risk of cardiovascular disease, clinical studies have suggested that cardiac- specific outcomes of patients with end-stage renal disease were better with AVF compared with other dialysis modal- ities. This study uses a mouse model of AVF to study the structural, functional, and molecular correlates of AVF-induced cardiac remodeling. It finds that AVF causes an adaptive cardiac hypertrophy without functional decline or fibrosis. Tran- scriptional correlates suggest an electrical remodeling and the upregulation of proangiogenic, procardiogenic, and pro- survival factors, implying that AVF-induced cardiac hypertrophy is potentially cardioprotective, but also arrhythmogenic.