Epicardial Adipose Tissue Accumulation Confers Atrial Conduction Abnormality

Area of Science:

• Cardiology
• Electrophysiology
• Molecular Biology

Background:

• Epicardial adipose tissue (EpAT) accumulation is linked to atrial fibrillation (AF) progression and management challenges.
• The precise role of local EpAT in AF pathogenesis and its underlying electrophysiological, cellular, and molecular mechanisms are not fully understood.

Purpose of the Study:

• To elucidate the mechanisms by which EpAT influences the atrial substrate in the context of AF.

Main Methods:

• Utilized computed tomography and epicardial electrophysiological mapping to quantify EpAT and assess its association with the atrial electrophysiological substrate.
• Histological analysis of atrial appendages characterized EpAT infiltration, fibrosis, and gap junction distribution.
• Co-culture experiments and proteomic analyses investigated the paracrine effects of EpAT on cardiomyocyte electrophysiology and identified molecular mediators.

Main Results:

• Increased local EpAT volume correlated with slowed atrial conduction, increased electrogram fractionation, and fibrosis.
• Myocardial EpAT infiltration led to greater atrial conduction heterogeneity and connexin-40 lateralization.
• EpAT-secreted factors in co-culture studies impaired cardiomyocyte conduction velocity and intermyocyte electromechanical integrity.

Conclusions:

• Atrial pathophysiology is significantly influenced by local EpAT accumulation and infiltration.
• An EpAT-cardiomyocyte paracrine axis contributes to AF, alongside disruption of myocardial architecture.
• Focal adhesion group proteins are identified as potential novel contributors to the arrhythmogenic atrial substrate.