Cardiac dysfunction is associated with indices of brain atrophy and cognitive impairment in heart failure with reduced ejection fraction

Cardiac dysfunction in heart failure with reduced ejection fraction (HFrEF) may contribute to brain atrophy and cognitive decline beyond that which is typical of healthy aging. This study tested the hypothesis that HFrEF would be associated with regionally unique brain remodeling and impaired cognitive performance independent of age. Furthermore, that cardiac index and clinical markers of HFrEF severity would predict brain remodeling and cognition with age and HFrEF, respectively. Cardiac function and brain morphology were assessed using magnetic resonance imaging in young healthy adults (24 ± 6 yr), older healthy adults (60 ± 6 yr), and patients living with HFrEF (59 ± 6 yr). The Montreal Cognitive Assessment was administered to assess cognition. Gray matter volume (GMV) (young: 492 ± 24, old: 456 ± 24, HFrEF: 433 ± 32 cm³, <i>P</i> ≤ 0.05) and cortical thickness (young: 2.44 ± 0.07, old: 2.33 ± 0.08, HFrEF: 2.22 ± 0.10 mm, <i>P</i> < 0.01) were lower with age and lowered further with HFrEF. Regional analysis revealed a unique pattern of atrophy with HFrEF. Whereas age had little effect on cortical curvature (<i>P</i> = 0.60), it was greater in HFrEF (young: 0.127 ± 0.003, old: 0.128 ± 0.003, HFrEF: 0.136 ± 0.005 mm^-1, <i>P</i> < 0.01). Cardiac index was the best correlate of brain atrophy and cognitive performance with age (<i>R</i> = 0.33-0.47; <i>P</i> < 0.05). However, EF and end systolic volume index were better correlates of brain atrophy and cognitive performance in HFrEF (<i>R</i> = -0.50-0.49; <i>P</i> ≤ 0.05). These data indicate that lower GMV and cortical thickness in HFrEF are not merely an acceleration of age-related declines but reflect a unique pattern of brain atrophy and remodeling. In addition, classic markers of HF severity may be better predictors of pathological brain remodeling than reduced cardiac index.<b>NEW & NOTEWORTHY</b> Lower gray matter volume, and cortical thinning in heart failure are regionally dependent, and independent of age. Patients living with heart failure had higher cortical curvature, but older adults did not. Lower gray matter volume, cortical thinning, and cognitive impairment were associated with markers of cardiac dysfunction, with ejection fraction, and end systolic volume index being better predictors among the older and heart failure cohort than cardiac index.