Aberrant Glymphatic System Function in Chronic Heart Failure with Preserved Ejection Fraction

Cognitive dysfunction is frequently observed in chronic Heart Failure with preserved Ejection Fraction (HFpEF) patients, while the underlying neuropathological basis remains incompletely characterized. This study aimed to demonstrate aberrant glymphatic system function in chronic HFpEF and its association with cognitive ability.

We proposed a multimodal neuroimaging model combining the Analysis of Perivascular Space Index (ALPS-index), Choroid Plexus Volume (CPV), and Perivascular Space (PVS) for early detection of HFpEF-related brain injury. Thirty-one chronic HFpEF patients and 32 Healthy Controls (HCs) were enrolled and underwent brain MRI and cognitive function tests. Associations between glymphatic markers, cognitive scores, and cardiac function were analyzed.

The ALPS-index in patients with chronic HFpEF was significantly decreased (p = 0.017), and the volumes of CPV and PVS were larger (p = 0.004; p = 0.011). Furthermore, correlation analysis revealed a significant positive correlation between CPV and TMT-B scores (r = 0.634, p < 0.001), and CPV showed an inverse correlation with Left Ventricular Ejection Fraction (LVEF) (r = -0.542, p = 0.003) and Fractional Shortening (FS) (r = -0.508, p = 0.006). The diagnostic efficacy of the multimodal model (ALPS-index + CPV + PVS) was improved compared to a single marker (AUC = 0.79 vs. AUC = 0.75 for CPV alone).

These findings suggest that chronic HFpEF is associated with glymphatic dysfunction, as reflected by a reduced ALPS-index and enlarged CPV and PVS. The correlation between CPV and both cognitive and cardiac parameters highlights a potential heart-brain axis mechanism. The multimodal imaging approach demonstrated promising diagnostic value, supporting its potential utility for early detection of cerebral involvement in HFpEF.

Chronic HFpEF may induce dysfunction of the glymphatic system, which is manifested as decreased ALPS-index, enlarged CPV and PVS, and is associated with cognitive decline and cardiac dysfunction. Multimodal neuroimaging markers may serve as promising neuroimaging markers for the early identification of chronic HFpEF-related cognitive impairment.