Spatial Metabolic Profiling of Human Atrial Tissue in Atrial Fibrillation Using DESI-MSI: An Exploratory Pilot Study.

Abstract

Background: Structural remodeling and atrial fibrosis are hallmarks of atrial fibrillation (AF), yet molecular alterations associated with atrial remodeling remain incompletely characterized, particularly their spatial distribution within human atrial tissue. Desorption Electrospray Ionization Mass Spectrometry Imaging (DESI-MSI) enables spatially resolved metabolic profiling of tissue sections and may provide insight into metabolic alterations associated with atrial remodeling in AF. This study investigated whether DESI-MSI could identify distinct metabolic signatures in atrial tissue from patients with AF.

Methods: In this exploratory pilot study, atrial tissue samples from 10 patients undergoing cardiac surgery (4 with AF and 6 controls) underwent DESI-MSI analysis across an m/z range of 50-1200, followed by histologic assessment with hematoxylin-eosin staining. Metabolic profiles were analyzed using principal component analysis (PCA) and linear discriminant analysis (LDA) to explore group-specific metabolic patterns.

Results: Histologic evaluation demonstrated minimal fibrosis without significant differences between AF and control samples. In contrast, DESI-MSI identified distinct metabolic features associated with AF. Arachidonic acid (m/z 303.2) and phosphatidylinositol species (m/z 885.5) demonstrated spatial correspondence with myocardial architecture and contributed to metabolic separation between groups. Exploratory supervised multivariate analysis showed partial separation between AF and control spectra, while LD loading plots identified differential lipid-related ion patterns associated with AF samples.

Conclusions: In this exploratory pilot cohort, DESI-MSI demonstrated preliminary metabolic differences between AF and control atrial tissues despite limited histologic remodeling. These findings should be considered hypothesis-generating and will require validation in larger, adequately matched cohorts integrating metabolic, histologic, and clinical phenotypes. Although they do not establish that metabolic remodeling precedes fibrosis, they raise the possibility that DESI-MSI may detect metabolic differences in atrial tissue exhibiting minimal histologic remodeling.