Atorvastatin Prevents Early Lipotoxic Remodeling in Right Ventricular Pacing–Induced Cardiomyopathy

Background Right ventricular (RV) pacing can induce metabolic and structural alterations in left ventricular (LV) myocardium, including lipid accumulation, glycogen depletion, and increased endoplasmic reticulum (ER) stress. This study evaluated protective effects of atorvastatin on RV pacing–induced metabolic dysfunction. Methods Fifteen male Lanyu miniature pigs were randomized into sham control (n=5), RV pacing (n=5), and RV pacing with atorvastatin treatment (RVS pacing, n=5) groups. RV pacing was achieved via ventricular lead implantation at RV outflow tract, followed by complete atrioventricular block, with ventricular pacing maintained at least 80 beats/min in DDDR mode to provide atrial-synchronous ventricular pacing while allowing atrial sensing or pacing. The RVS pacing group received atorvastatin (40 mg/day) starting two weeks before surgery until euthanasia at six months. Metabolic, histological, and molecular parameters were assessed in LV myocardial tissue. Results Compared with sham controls, RV pacing significantly increased myocardial lipid accumulation, with higher triglyceride (TG: 2.43±0.17 vs. 1.74±0.14 μg/mg, P<0.01) and diacylglycerol (DAG: 2902±567.7 vs. 977.5±182.5 μg/mg, P<0.01) levels, and significantly reduced glycogen content (0.09±0.03 vs. 0.21±0.03 μg/mg, P<0.05). ER stress markers BiP and cleaved caspase-9 were markedly increased in RV pacing group (P<0.0001). Atorvastatin significantly reduced lipid accumulation (TG: 1.83±0.08 μg/mg; P<0.05), ER stress, and apoptosis, but did not significantly restore glycogen levels. Conclusion RV pacing induces lipid accumulation, glycogen loss, and increased ER stress in the LV myocardium. Atorvastatin partially mitigated these effects by normalizing fatty acid metabolism and reducing ER stress and apoptosis, suggesting a potential role in attenuating early/subclinical RV pacing–induced metabolic remodeling.