Heart failure-induced brain myelin changes and differences between sexes.

Area of Science:

• Neuroimaging
• Cardiology
• Neurology

Background:

• Heart failure (HF) is linked to brain dysfunction affecting autonomic, respiratory, mood, and cognitive functions.
• Previous studies indicate tissue volume loss and altered brain metabolites in HF patients.
• The specific impact of HF on brain myelin integrity and sex-based differences remains unclear.

Purpose of the Study:

• To investigate regional brain subcortical and white matter myelin integrity in HF patients compared to controls.
• To examine sex-specific differences in brain myelin integrity among HF patients.

Main Methods:

• Acquired T1- and T2-weighted MRI scans from 63 HF patients and 129 controls using a 3.0-Tesla scanner.
• Computed ratio maps from T1- and T2-weighted images, normalized, smoothed, and compared between groups using ANCOVA.
• Statistical analyses included covariates for age and sex, with significance thresholds set at p < .010 (FDR) for group comparisons and p < .005 (uncorrected) for sex comparisons within HF.

Main Results:

• HF patients demonstrated reduced myelin integrity in multiple brain regions, including the amygdala, hippocampus, cingulate, insula, cerebellum, prefrontal cortices, and white matter, compared to controls.
• Female HF patients exhibited greater myelin injury in the parietal, prefrontal, frontal, hippocampus, amygdala, pons, cerebellum, insula, and corpus callosum compared to male HF patients.
• Overall, HF compromised subcortical and white matter myelin integrity, particularly in regions regulating autonomic, respiratory, mood, and cognitive functions, with females showing more pronounced changes than males.

Conclusions:

• Heart failure leads to compromised subcortical and white matter myelin integrity, affecting critical brain functions.
• Significant sex differences exist, with female HF patients experiencing more extensive brain myelin damage.
• These findings offer a structural explanation for more severe symptoms observed in female HF patients compared to males with similar disease severity.