Association of Glymphatic System Dysfunction with Cardiac Injury and Cognitive Impairment in Heart Failure: A Multimodal MRI Study.

Objective: 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.

Methods: 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.

Results: 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.

Conclusions: 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.