Abstract Body: Introduction: The brain's glymphatic system is crucial for clearing metabolic waste and maintaining balanced fluid circulation within the brain. Enlarged perivascular spaces in the basal ganglia (EPVS-BG) are markers of hypertensive cerebral small vessel disease (HTN-cSVD) due to glymphatic system dysfunction. Atrial fibrillation (AF) has been proposed to increase the wall shear stress and blood pressure in the lenticulostriate arteries (LSA), both potentially contributing to glymphatic dysfunction and cSVD development. We hypothesized that a higher AF burden is related to the presence of a severe degree EPVS-BG, potentially through the hemodynamic effects of AF on LSAs.
Methods: We analyzed data from 641 AF patients who had no clinical history of stroke or neurodegenerative disease and received brain MRIs with appropriate sequences at a tertiary care center. Neuroimaging data were collected by a stroke neurologist blinded to the clinical data. AF load was classified as lower-burden (paroxysmal/persistent AF) or higher-burden (longstanding persistent/permanent AF). The imaging outcome variables were the presence of severe EPVS-BG (>20 on one side of the brain), Fazekas score, atrophy score, lacunes and microbleeds (MB) in deep/lobar locations (FIGURE). The multivariable model was adjusted for all variables with p<0.1 in univariate analysis.
Results: The mean age of the 641 AF patients was 74+10 years, 242 (37.8%) were female, and 123 (19.2%) had a higher AF burden. Severe EPVS-BG were found in 15.9%, deep lacunes in 24.5%, and deep MBs in 8.3%. In univariate analyses, the presence of severe EPVS-BG was associated with a higher AF burden (31.4% vs 16.9%, p<0.001), Fazekas score (p<0.001), atrophy score (p<0.001), higher counts of deep lacunes (p<0.001), and deep MBs (p=0.002). In multivariable analyses, higher AF burden remained an independent predictor of EPVS-BG (OR=2, 95% CI 1.14-3.5, p=0.015), together with Fazekas score, deep lacunes, and deep MBs, after adjusting for age, sex, serum creatinine, sleep apnea, hypertension, smoking status, lobar lacunes and MBs.
Conclusion: Our results show that AF burden is independently associated with severe EPVS-BG, even after adjusting for important imaging markers of HTN-cSVD (leukoaraiosis, deep lacunes and deep MB). Higher AF burden can independently contribute to glymphatic dysfunction around the LSAs resulting in parenchymal brain injury, in addition to the known harmful effects of hypertension on these vessels.