Galectin-3 Regulates Atrial Fibrillation Remodeling and Predicts Catheter Ablation Outcomes

• Intracardiac serum galectin (Gal)-3 levels are shown to be greater in patients with persistent than paroxysmal atrial fibrillation (AF), and the Gal-3 level was an independent predictor of AF recurrences after a single ablation procedure.
• In a sheep model, the Gal-3 inhibitor GM-CT-01 (GMCT) reduced atrial fibroblast proliferation in vitro.
• GMCT mitigated atrial dilation, myocyte hypertrophy, fibrosis, and the expected increase in DF during transition to persistent AF.
• GMCT-treated sheep hearts had longer action potential durations, and fewer rotors and wavebreaks during AF than control.
• GMCT increased the number of spontaneous AF terminations and reduced overall AF burden.

SummaryAtrial fibrillation (AF) usually starts as paroxysmal but can evolve relentlessly to the persistent and permanent forms. However, the mechanisms governing such a transition are unknown. The authors show that intracardiac serum levels of galectin (Gal)-3 are greater in patients with persistent than paroxysmal AF and that Gal-3 independently predicts atrial tachyarrhythmia recurrences after a single ablation procedure. Using a sheep model of persistent AF the authors further demonstrate that upstream therapy targeting Gal-3 diminishes both electrical remodeling and fibrosis by impairing transforming growth factor beta–mediated signaling and reducing myofibroblast activation. Accordingly, Gal-3 inhibition therapy increases the probability of AF termination and reduces the overall burden of AF. Therefore the authors postulate that Gal-3 inhibition is a potential new upstream therapy to prevent AF progression.

Visual AbstractFigure optionsDownload high-quality image (177 K)Download as PowerPoint slide