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Heart failure (HF) patients show cognitive and mood impairments, including short-term memory loss and depression, that have an adverse impacting on quality of life and self-care management. Brain regions, including the hippocampus, a structure significantly involved in memory and mood, show injury in HF, but the integrity of specific hippocampal subregions is unclear.To assess regional hippocampal volume loss, we evaluated 17 HF patients (mean age ± SD, 54.4 ± 2.0 years; 12 male, left ventricular ejection fraction 28.3 ± 6.8%; New York Heart Association class II/III 94%/6%) and 34 healthy control subjects (52.3 ± 1.3 years; 24 male) using high-resolution T1-weighted magnetic resonance imaging and evaluated localized surface changes with morphometric procedures. Hippocampi were manually outlined, and volumes calculated from normalized tracings. Volume differences between groups were assessed by two-sample t-tests, and regional differences were assessed by surface morphometry. Patients with HF exhibited smaller hippocampal volumes than controls (right 3060 ± 146 mm3 vs. 3478 ± 94 mm3, P = 0.02; left 3021 ± 145 mm3 vs. 3352 ± 98 mm3, P = 0.06). Volume reductions were detected principally in CA1, an area integral to an array of learning and memory functions, as well as in mid to posterior CA3 and subiculum.The hippocampus shows regional volume reduction in HF, which may contribute to short-term memory loss and depression associated with the condition.