Frequent Premature Atrial Contractions Lead to Adverse Atrial Remodeling and Atrial Fibrillation in a Swine Model

• DOI: 10.1161/circulationaha.123.065874
• Publication Date: 2023-11-23T10:08:38Z
• Authors: Satoshi Higuchi; Aleksandr Voskobo...; Sung Il Im; Adam Lee; Jeffrey Olgin; Ayla Arbil; Junaid Afzal; Gregory M. Marcus; Carol Stillson; Dwight Bibby; Theodore Abraham; Emily Wilson; Edward P. Gersten...
• Keywords: Atrium (architecture); Premature atrial contraction

BACKGROUND: Frequent premature atrial complexes (PACs) are associated with future incident fibrillation (AF), but whether PACs contribute to development of AF through adverse remodeling has not been studied. This study aimed explore the effect frequent from different sites on in a swine model. METHODS: Forty underwent baseline electrophysiologic studies and echocardiography followed by pacemaker implantations paced (50% burden) at 250-ms coupling intervals for 16 weeks 4 groups: (1) lateral left atrium (LA) coronary sinus (Lat-PAC; n=10), (2) interatrial septal (Sep-PAC; (3) regular LA pacing 130 beats/min (Reg-130; (4) controls without (n=10). At final study, repeat were performed, tissue histology molecular analyses focusing fibrotic pathways. RESULTS: Lat-PACs longer P-wave duration (93.0±9.0 versus 74.2±8.2 58.8±7.6 ms; P <0.001) greater echocardiographic mechanical dyssynchrony (57.5±11.6 35.7±13.0 24.4±11.1 compared Sep-PACs controls, respectively. After weeks, led slower conduction velocity (1.1±0.2 1.3±0.2 [Sep-PAC] 1.3±0.1 [Reg-130] 1.5±0.2 [controls] m/s; significant change ERP. The Lat-PAC group had significantly increased percentage fibrosis upregulated levels extracellular matrix proteins (lysyl oxidase collagen 1 8), as well TGF-β1 (transforming growth factor–β1) signaling (latent monomer phosphorylation/total ratio SMAD2/3; <0.05). longest inducible (terminal baseline: 131 [interquartile range 30, 192] seconds [6, 26] 22 [11, 64] −1 [−16, 7] [controls]; <0.001). CONCLUSIONS: In this model, resulted structural heightened propensity AF. originating produced induced than septal-origin PACs. These data provide evidence that can cause AF, location ectopic may be clinically meaningful.