Right ventricular (RV) pacing-induced cardiomyopathy (PICM) occurs in ~30% of patients with RV leads. Here, we evaluate the long-term effects of restoring antegrade conduction with a biological pacemaker in a porcine model of RV PICM.
In pigs with complete atrioventricular (AV) block, TBX18 was injected into the His bundle region in either of two experimental protocols: protocol A sought to prevent PICM, while protocol B sought to reverse PICM. In protocol A, we injected adenoviral vectors expressing TBX18 (or the reporter construct GFP) after AV node ablation, and followed the animals for 8 weeks. In protocol B, PICM was established by AV node ablation and 4 weeks of electronic RV pacing, at which point TBX18 was injected in the His bundle region.
In protocol A, TBX18 biological pacing led to superior chronotropic support (62.4±3 bpm vs 50.4±0.4 bpm, p=0.01), lower back-up pacemaker utilization (45±2.6% vs 94.6±1.4%, p=0.001), and greater ejection fraction (EF; 58.5±1.3% vs 46.7±2%, p=0.001). In protocol B, fullblown RV PICM was evident 4 weeks after complete AV block in both groups; subsequent intervention led to higher mean HR(56±2 bpm vs 50.10±0.4bpm, p=0.05), less backup pacemaker utilization(53±8.2% vs 95±1.6%, p=0.003), and a greater EF(61.7±1.3 vs 49±1.6%, p=0.0003) in TBX18-injected animals vs. GFP controls.
In a preclinical model, pacemaker-induced cardiomyopathy can be prevented, and reversed, by restoring antegrade conduction with TBX18 biological pacing.