Heart failure associations with cerebral structure: combined analysis from the Multi‐Ethnic Study of Atherosclerosis (MESA) and the SECRET‐II trial of heart failure with preserved ejection fraction

Abstract

AbstractBackgroundHeart failure (HF) with preserved ejection fraction (HFpEF) is the most common form of HF in adults 65 and older, but little is known about its relationship with neurocognitive outcomes. We compared brain magnetic resonance imaging (MRI) markers in older adults across stages of preclinical HF and clinical HFpEF.MethodAll participants completed baseline HF evaluation of risk factors, echocardiography, electrocardiography, and cardiopulmonary exercise by ACC/AHA stages; 3T brain MRI; and cognitive testing using harmonized protocols and teams at Wake Forest School of Medicine (2016‐2021). MESA participants without symptomatic HF were assigned to: Stage 0, no risk factors for HF (n = 30); Stage A, risk factors for HF without cardiac structural abnormalities (n = 111); or Stage B, abnormal cardiac structure or function without HF symptoms (n = 66). Participants with stable clinical HFpEF were recruited from the SECRET‐II trial and assigned to Stage C (n = 43). We compared intracranial volume‐adjusted total gray matter (GM), hippocampal, and white matter hyperintensity lesion (WMH) volumes across HF stages using multivariable linear regression adjusted for age, sex, and race, and report standardized least‐squares (LS) means estimates in SD units with 95% CI and Dunnett‐adjusted p‐values (referent = Stage 0).ResultThe combined sample (N = 250) was aged 72±7 years, 64% female, 47% white, and completed 15±3 years of education. Participants with Stage C HFpEF were younger (69±5 vs. 73±7 years, p<0.001) and more likely to be female (85% vs. 59%, p<0.001) than participants in lower stages. Stage B and Stage C participants had significantly lower GM volume than Stage 0 (0.38 [0.07, 0.69] vs. ‐0.12 [‐0.33, 0.09] in Stage B, p = 0.019; ‐0.36 [‐0.64, ‐0.09] in Stage C HFpEF, p = 0.001; Figure A), and Stages A‐C had non‐significant trends toward lower hippocampal volume (Stage 0 vs. Stage C p = 0.053; Figure B) and greater WMH volume (Stage 0 vs. Stages A‐C combined p = 0.073; Figure C). There were no interactions by sex or race.ConclusionIn this combined analysis from harmonized and diverse cohorts, higher HF stages and clinical HFpEF were associated with significantly lower gray matter volume. Observed trends toward lower hippocampal volume and higher WMH volume in HF Stages A‐C warrant further investigation.