Left atrial remodeling and microstructural damage in the internal capsule in heart failure: a comparison based on left atrial maximum volume index stratification

Background Heart failure (HF) patients face increased risk of cardiogenic cerebral embolism (CCE) and silent brain infarction—major drivers of disability and death. Left atrial (LA) remodeling promotes thrombus formation, the key substrate for CCE. Left atrial maximum volume index (LAVI) is the gold-standard measure of LA remodeling and an independent CCE risk factor in HF. Conventional neuroimaging cannot detect ultra-early white matter (WM) changes. However, the link between LA remodeling and WM integrity in HF remains unclear. Purpose To characterize whole-brain WM microstructural alterations in HF patients stratified by LAVI using diffusion tensor imaging (DTI), and to identify an imaging biomarker for early CCE risk detection. Methods We prospectively enrolled 51 patients with HF and 34 non-HF controls, rigorously matched for age, sex, and cardiovascular risk factors. All participants underwent brain DTI. Whole-cohort Tract-Based Spatial Statistics(TBSS) with Threshold-Free Cluster Enhancement (TFCE) correction was performed to identify core WM regions showing the most significant microstructural differences between the HF and control groups. In a sub-cohort (24 HF, 11 controls) who also underwent cardiac magnetic resonance (CMR) for LAVI quantification, HF patients were divided by median LAVI (48.10 mL/m²) into low-LAVI (n=12) and high-LAVI (n=12) subgroups. From the significant core cluster identified in the whole-cohort analysis, DTI-derived metrics, including fractional anisotropy (FA), were extracted. These metrics were compared across the three groups (controls, low-LAVI HF, high-LAVI HF) using one-way ANOVA with Tukey's HSD post-hoc test. Results Compared with controls, HF patients exhibited widespread WM disruption, characterized by significantly lower FA and higher diffusivity in multiple brain regions (all P<0.05). The most significantly affected core cluster was localized in the left hemisphere, predominantly involving the retrolenticular part of the internal capsule—a territory highly vulnerable to CCE—and extending into the inferior fronto-occipital fasciculus and the fornix (η²=0.496). Both HF subgroups showed significantly lower FA in this cluster compared with controls (high-LAVI: mean difference = -0.0327, P<0.0001; low-LAVI: mean difference = -0.0251, P=0.0007). The reduction in FA was more pronounced in the high-LAVI subgroup than in the low-LAVI subgroup. Conclusion In patients with HF, LA remodeling is associated with widespread WM microstructural damage, most prominently within the internal capsule. This region may serve as a high-sensitivity target for CCE-related microembolic injury. FA reduction in the internal capsule could represent a sensitive imaging biomarker for early identification of HF patients at heightened risk for CCE.