Reduced resting global cerebral blood flow has been previously detected in association with heart failure (HF), but it is not clear whether there are brain regions that could be specifically affected by those brain perfusion deficits. The authors used a fully automated, voxel-based image analysis method to investigate, across the entire cerebral volume, the presence of resting regional cerebral blood flow (rCBF) abnormalities in HF patients compared to healthy controls. rCBF was evaluated with 99mTc-single-photon emission computed tomography in 17 HF patients (New York Heart Association functional class II or III) and 18 elderly healthy volunteers. Voxel-based analyses of rCBF data were conducted using the statistical parametric mapping software. Significant rCBF reductions in HF patients relative to controls (P<.05, corrected for multiple comparisons) were detected in 2 foci, encompassing, respectively, the left and right precuneus and cuneus and the right lateral temporoparietal cortex and posterior cingulated gyrus. In the HF group, there was also a significant direct correlation between the degree of cognitive impairment as assessed using the Cambridge Mental Disorders of the Elderly Examination and rCBF on a voxel cluster involving the right posterior cingulate cortex and precuneus, located closely to the site where between-group rCBF differences had been identified. These preliminary findings indicate that posterior cortical areas of the brain may be particularly vulnerable to brain perfusion reductions associated with HF and suggest that functional deficits in these regions might be relevant to the pathophysiology of the cognitive impairments presented by HF patients.