Targeted Intra-Atrial Delivery of GMP-Grade Human Extracellular Vesicles Prevents Inflammation-Driven Postoperative Atrial Fibrillation in Pigs

Targeted intra-atrial delivery of GMP-grade human cardiac extracellular vesicles (EVs) was evaluated for prevention of postoperative atrial fibrillation (AF). EVs were manufactured under serum-free, xenogen-free GMP-compatible conditions and tested in rat and porcine sterile pericarditis models. In rats, intra-atrial EV delivery resulted in selective atrial retention without systemic toxicity. In pigs, EV administration was technically feasible, well tolerated, and completely prevented spontaneous AF while significantly reducing inducible AF. EV therapy also attenuated atrial inflammation and fibrosis without adverse end-organ effects. These findings support localized cardiac EV therapy as a first-in-human-ready, disease-modifying biologic strategy for postoperative AF prevention.