Atrial Cardiomyopathy in Atrial Fibrillation: A Multimodal Diagnostic Framework

Atrial fibrillation (AF) is increasingly recognized as the clinical manifestation of an underlying atrial disease process rather than a purely electrical disorder. This evolving paradigm has given rise to the concept of atrial cardiomyopathy (AtCM), encompassing structural, electrical, contractile, and molecular remodeling of the atrial myocardium that contributes to AF initiation, maintenance, and progression. Although consensus definitions of AtCM now exist, its integration into clinical practice remains limited, with AF management still largely guided by arrhythmic patterns rather than substrate characterization. This review synthesizes current diagnostic strategies for AtCM within the context of AF, emphasizing a multimodal approach. We outline advances in cardiac imaging-including echocardiography, cardiac magnetic resonance, and computed tomography-for detailed assessment of atrial morphology, function, and fibrosis. Electroanatomic mapping is discussed as a key invasive tool for substrate localization, while electrocardiographic indices such as P-wave morphology and dispersion serve as accessible surrogates of electrical remodeling. In parallel, we examine the role of circulating biomarkers and emerging genomic, transcriptomic, and epigenomic markers in refining disease phenotyping. Despite promising progress, significant challenges remain. Standardization of imaging protocols, validation of biomarker thresholds, and integration of artificial intelligence tools are needed to enhance clinical utility. A diagnostic framework informed by atrial substrate assessment may support more tailored therapeutic decision-making in AF. Future research should prioritize the harmonization of diagnostic criteria and explore how substrate profiling in AF may refine risk stratification and improve clinical outcomes.