Low-intensity pulsed ultrasound attenuates atrial remodelling and atrial fibrillation after myocardial infarction: an experimental pre-clinical study.

AIMS: Post-infarct atrial remodelling creates a substrate for atrial fibrillation (AF), yet no cardiac-specific, non-invasive therapy targets this process. Low-intensity pulsed ultrasound (LIPUS) limits ventricular remodelling in preclinical models, but its impact on atrial remodelling and AF after myocardial infarction (MI) is unknown. METHODS AND RESULTS: Myocardial infarction was induced in rats by surgical ligation of the left coronary artery, whereas a separate AF rat model was created by daily tail-vein injections of acetylcholine/calcium chloride (CaCl₂) for 28 days. Low-intensity pulsed ultrasound treatment did not cause significant structural, functional, or electrophysiological changes in the atrial tissue of healthy rats. In MI rats, LIPUS markedly attenuated atrial electrical remodelling, fibrosis, and inflammation, thereby reducing AF susceptibility. Transcriptomic analysis demonstrated a potential role of Adam19/transforming growth factor-β (TGF-β)/Smad2/3 signalling in response to LIPUS treatment, whereas activation of Adam19/TGF-β/Smad2/3 signalling worsened fibrosis and abolished the antiarrhythmic benefit of LIPUS. Similar antifibrotic and antiarrhythmic effects were reproduced in the acetylcholine/CaCl₂ AF model, underscoring LIPUS as a promising non-invasive approach to attenuate AF after MI. CONCLUSION: In preclinical post-MI models, LIPUS attenuated atrial structural and electrical remodelling and lowered AF susceptibility, plausibly via modulation of an Adam19/TGF-β/Smad2/3 signalling cascade. These findings are promising but preliminary; priorities include determining whether the atrial effects are direct or secondary to ventricular remodelling and altered haemodynamics, confirming mechanisms across models, defining dose-response and safety and validating efficacy and translational relevance in large-animal studies and early-phase trials before any clinical application.