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AimsThis systematic review aimed to study the hippocampal and frontal changes of heart failure (HF) patients and HF animal models with cognitive impairment or depression.MethodsA systematic review of the literature was conducted independently by reviewers using PubMed, Web of Science, Embase, and the Cochrane Library databases.Results and conclusions30 studies were included, involving 17 pieces of clinical research on HF patients and 13 studies of HF animal models. In HF patients, the hippocampal injuries were shown in the reduction of volume, CBF, glucose metabolism, and gray matter, which were mainly observed in the right hippocampus. The frontal damages were only in reduced gray matter and have no difference between the right and left sides. The included HF animal model studies were generalized and demonstrated the changes in inflammation and apoptosis, synaptic reduction, and neurotransmitter disorders in the hippocampus and frontal lobes. The results of HF animal model studies complemented the clinical observations by providing potential mechanistic explanations of the changes in the hippocampus and frontal lobes.