Glymphatic dysfunction, a critical pathway to cognitive impairment, remains underexplored in heart failure (HF). This study investigated glymphatic dysfunction in patients with HF and the relationship between cardiac injury and cognitive performance.46 HF patients and 39 age- and sex-matched healthy controls (HCs) underwent brain MR to assess glymphatic markers: choroid plexus (CP) volume, perivascular space (PVS) score, white matter fractional free water (FW), diffusivity along perivascular spaces (ALPS), blood-oxygen-level-dependent (BOLD) signals, and cerebrospinal fluid (CSF) coupling. Group differences were analyzed, and same-day cardiac MR in HF patients assessed cardiac injury markers. Correlation, regression, and mediation analyses explored associations between glymphatic markers, cardiac injury markers, and cognition.Patients with HF exhibited significantly higher CP volume, PVS scores, and FW, alongside a lower mean ALPS index and BOLD-CSF coupling than HCs (all P<0.05). Montreal Cognitive Assessment (MoCA) score correlated positively with the mean ALPS index (r=0.479, Padjust=0.014) and inversely with basal ganglia PVS score (r=-0.462, Padjust=0.033) and BOLD-CSF coupling (r=-0.398, Padjust=0.043). Among cardiac MRI parameters, stroke volume (SV) and SV index (SVI) correlated significantly with the mean ALPS index (r=0.419, Padjust=0.020; r=0.448, Padjust=0.014). Mediation analysis showed that the mean ALPS index mediated the correlation between SV/SVI and MoCA scores.Patients with HF exhibit glymphatic dysfunction, with the mean ALPS index closely correlated to cardiac function and cognition. Cardiac injury-related glymphatic dysfunction in patients with HF may link to cognitive impairment.Copyright © 2025 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.