Shorter Premature Atrial Complex Coupling Interval Leads to Mechanical Dysfunction, Fibrosis, and AF in Swine.

Background: We have previously shown that dyssynchronous premature atrial complexes (PACs) from the lateral left atrium (LA) lead to greater atrial mechanical dysfunction, remodeling, and sustained atrial fibrillation (AF) than synchronous PACs from the interatrial septum. However, the impact of PAC coupling interval (CI) on atrial remodeling is unclear.

Objectives: This study sought to explore the effect of PAC CI on atrial mechanics and remodeling in the swine model.

Methods: A 2-phase in vivo study was conducted. In the phase 1 acute study, 5 swine underwent acute invasive hemodynamics and echocardiography while delivering single-paced atrial extrastimuli with CIs varying from 450 ms to 200 ms. Peak LA longitudinal strain and intra-LA dyssynchrony were assessed with 2-dimensional strain echocardiography while LA and aortic pressure were directly measured. In the phase 2 chronic study, a group exposed to paced bigeminy from the lateral LA for 16 weeks with a short CI of 250 ms (Short-PAC, n = 10) was compared with groups with PACs at a long CI of 400 ms (Long-PAC, n = 5) and a nonpaced control group (CTRL, n = 10). Detailed electrophysiology and echocardiography studies were performed with histologic quantification of LA fibrosis at baseline and prior to sacrifice.

Results: Phase 1 revealed that as PAC CI shortened, peak LA strain decreased (P = 0.003) and LA dyssynchrony increased (P < 0.001). Phase 2 showed that after 16 weeks of PACs, the Short-PAC group had greater LA dilation (terminal baseline: 5.9 ± 1.2 cm² vs Long-PAC 3.9 ± 0.5 cm² vs CTRL 0.9 ± 0.4 cm²; P < 0.001) and reduced peak LA strain during sinus rhythm (terminal baseline: -17.3 ± 3.2% vs Long-PAC -12.1 ± 2.1% vs CTRL -0.7 ± 4.2%; P < 0.001). The short-PAC group had a more LA fibrosis (8.6 ± 1.0% vs Long-PAC 6.8 ± 1.0% vs CTRL 4.0 ± 1.5%; P < 0.001) and higher AF inducibility (terminal baseline: 49.3 ± 13.0% vs Long-PAC 29.0 ± 6.4% vs CTRL 2.2 ± 16.2%; P < 0.001) than the other groups.

Conclusions: In this swine model, shorter PAC CI led to increased acute atrial mechanical dysfunction and dyssynchrony. Chronically, short-CI PACs led to greater atrial fibrosis and induced AF, suggesting that frequent, short-coupled PACs pose the highest risk for LA myopathy and AF. These insights underscore the importance of understanding the impact of PAC characteristics on atrial remodeling and arrhythmogenesis.