Atrial 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.
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.