Multimodal MRI reveals cortical triple-hit and subcortical compensation in cognitively normal chronic heart failure patients

Background Chronic heart failure (HF) is an independent risk factor for cognitive impairment, with cerebral hypoperfusion serving as the core pathological pathway mediating HF-related brain dysfunction. Previous studies have largely relied on a single imaging modality and focused on HF patients with overt cognitive symptoms. However, systematic multi-modality imaging evidence integrating cerebral blood flow, brain structure, and function remains lacking in HF patients with normal cognitive function. Objective To investigate aberrant multi-modality brain imaging patterns in cognitively normal HF patients by combining arterial spin labeling (ASL), voxel-based morphometry (VBM), and regional homogeneity (ReHo), thereby providing evidence for the early identification of HF-related subclinical brain alterations. Methods Forty-seven patients with chronic HF diagnosed according to guideline criteria and 34 non-HF controls rigorously matched for age, sex, years of education, and underlying cardiovascular diseases were enrolled. All participants underwent cognitive assessments and 3.0T multi-modality MRI scanning to obtain cerebral blood flow (CBF), gray matter volume, and ReHo parameters. Between-group comparisons were performed using two-sample t-tests controlling for key covariates, followed by rigorous correction for multiple comparisons. The spatial overlap patterns of multi-modality abnormalities and their correlations with left ventricular ejection fraction (LVEF) were analyzed. Results No significant differences in cognitive scale scores were observed between the two groups (P > 0.05). Extensive brain imaging abnormalities were already present in HF patients: the left occipital cortex exhibited triple negative alterations characterized by decreased CBF, gray matter atrophy, and reduced ReHo (FDR correction, P < 0.001); the bilateral basal ganglia and cerebellum showed compensatory dual alterations with increased CBF and elevated ReHo (FDR correction, P < 0.001). Imaging metrics in the left occipital region were significantly positively correlated with LVEF (P < 0.01). Conclusions Characteristic multi-modality brain imaging alterations exist in cognitively normal HF patients, featuring a distinct pattern of "cortical negative alterations—subcortical compensation". Multi-modality MRI may provide sensitive biomarkers for the early identification of HF-related subclinical brain abnormalities.Figure2Figure1