Volumetric brain MRI signatures of heart failure with preserved ejection fraction in the setting of dementia

Abstract

Heart failure with preserved ejection fraction (HFpEF) is an important, emerging risk factor for dementia, but it is not clear whether HFpEF contributes to a specific pattern of neuroanatomical changes in dementia. A major challenge to studying this is the relative paucity of datasets of patients with dementia, with/without HFpEF, and relevant neuroimaging. We sought to demonstrate the feasibility of using modern data mining tools to create and analyze clinical imaging datasets and identify the neuroanatomical signature of HFpEF-associated dementia. We leveraged the bioinformatics tools at Vanderbilt University Medical Center to identify patients with a diagnosis of dementia with and without comorbid HFpEF using the electronic health record. We identified high resolution, clinically-acquired neuroimaging data on 30 dementia patients with HFpEF (age 76.9 ± 8.12 years, 61% female) as well as 301 age- and sex-matched patients with dementia but without HFpEF to serve as comparators (age 76.2 ± 8.52 years, 60% female). We used automated image processing pipelines to parcellate the brain into 132 structures and quantify their volume. We found six regions with significant atrophy associated with HFpEF: accumbens area, amygdala, posterior insula, anterior orbital gyrus, angular gyrus, and cerebellar white matter. There were no regions with atrophy inversely associated with HFpEF. Patients with dementia and HFpEF have a distinct neuroimaging signature compared to patients with dementia only. Five of the six regions identified in are in the temporo-parietal region of the brain. Future studies should investigate mechanisms of injury associated with cerebrovascular disease leading to subsequent brain atrophy.

Keywords: Clinical imaging; Data mining; Dementia; Electronic health record; Heart failure; Magnetic resonance imaging.

Fig. 1.

Inclusion and exclusion criteria protocol to identify patients with dementia and neuroimaging with and without heart failure.

Fig. 2.

Significant brain regions with atrophy associated with HFpEF in the setting of dementia. Top left: Left Accumbens Area; Top right: Right Amygdala; Middle left: Left Posterior Insula; Middle right: Right Angular Gyrus; Bottom left: Left Anterior Orbital Gyrus; Bottom right: Right Cerebellar White Matter.

Fig. 3.

Volumetric analysis of non-significant regions. All non-significant regions are shown on the y-axis with the corresponding log odds and 95% confidence intervals. These regions are ranked according to predicted effect size, where negative effect size signifies volume loss associated with heart failure with preserved ejection fraction (HFpEF). A full table of all sorted regions and corresponding effect sizes is shown in Supplement Table 1.

Fig. 4.

PheWAS analysis done on HFpEF dementia cohort. Significant clinical phenotypes associated with heart failure with preserved ejection fraction (HFpEF) in patients with dementia. Clinical phenomes are organized by organ system. A full table of significant clinical variables is shown in Supplement Table 2.