Statins and Pacing-Induced Atrial Myopathy: Unraveling Their Role in Atrioventricular Block Patients with Permanent Pacemakers

<b>Background:</b> Left atrial (LA) myopathy from interventricular dyssynchrony often precedes atrial fibrillation (AF) in atrioventricular block (AVB) patients with frequent right ventricular (RV) pacing, but the role of statin therapy in preventing LA myopathy and associated arrhythmias remains debated. <b>Objectives:</b> This study investigated the mechanisms of LA myopathy and the clinical outcomes of statin therapy in AVB patients with permanent pacemakers (PPMs). <b>Methods:</b> The study comprised an animal, cell, and clinical cohort study. In the animal study, 12 Lanyu miniature pigs were divided into sham control, RV pacing, and RV pacing plus atorvastatin groups to assess cardiac effects over six months. The cellular study used HL-1 atrial myocytes to evaluate fibrosis and protein expression after cyclic stretching. The clinical study included 2338 AVB patients with PPM, comparing statin and non-statin groups for AF incidence and outcomes using inverse probability of treatment weighting (IPTW). <b>Results:</b> In the animal model, atorvastatin did not affect LA size, function, or fibrosis. The cellular study showed increased fibrosis markers in both stretch and stretch plus atorvastatin groups compared to controls. In the PPM cohort, statin use did not significantly impact LA size, AF incidence (p=0.731), or CV mortality (p=0.129) over five years, but it was associated with significantly lower all-cause mortality (p=0.004) after IPTW adjustment. <b>Conclusion:</b> Statins do not appear to improve LA myopathy or reduce the incidence of associated atrial arrhythmias in the AVB population with PPMs.