BACKGROUND Right ventricular (RV) pacing-induced cardiomyopathy (PICM) occurs in ∼30% of patients with RV leads. This study evaluated the long-term effects of restoring antegrade conduction with a biological pacemaker in a porcine model of RV PICM. OBJECTIVES The goal of this study was to determine if antegrade biological pacing can attenuate RV PICM. METHODS In pigs with complete atrioventricular (AV) block, transcription factor T-box 18 (TBX18) was injected into the His bundle region in either of 2 experimental protocols: protocol A sought to prevent PICM, and protocol B sought to reverse PICM. In protocol A, we injected adenoviral vectors expressing TBX18 (or the reporter construct green fluorescent protein) after AV node ablation, and observed the animals for 8 weeks. In protocol B, PICM was established by using AV node ablation and 4 weeks of electronic RV pacing, at which point TBX18 was injected into the His bundle region. RESULTS In protocol A, TBX18 biological pacing led to superior chronotropic support (62.4 ± 3 beats/min vs. 50.4 ± 0.4 beats/min; p = 0.01), lower backup pacemaker utilization (45 ± 2.6% vs. 94.6 ± 1.4%; p = 0.001), and greater ejection fraction (58.5 ± 1.3% vs. 46.7 ± 2%; p = 0.001). In protocol B, full-blown RV PICM was evident 4 weeks after complete AV block in both groups; subsequent intervention led to higher mean heart rate (56 ± 2 beats/min vs. 50.1 ± 0.4 beats/min; p = 0.05), less backup pacemaker utilization (53 ± 8.2% vs. 95 ± 1.6%; p = 0.003), and a greater ejection fraction (61.7 ± 1.3% vs. 49 ± 1.6%; p = 0.0003) in TBX18-injected animals versus control animals. CONCLUSIONS In a preclinical model, pacemaker-induced cardiomyopathy can be prevented, and reversed, by restoring antegrade conduction with TBX18 biological pacing.

中文翻译：

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顺行传导在完全心脏传导阻滞中拯救右心室起搏诱发的心肌病

背景右心室 (RV) 起搏诱发的心肌病 (PICM) 发生在约 30% 的 RV 导联患者中。本研究评估了在 RV PICM 猪模型中使用生物起搏器恢复顺行传导的长期影响。目的 本研究的目的是确定顺行生物起搏是否可以减弱 RV PICM。方法 在具有完全房室 (AV) 阻滞的猪中，转录因子 T-box 18 (TBX18) 被注射到希氏束区域中的两种实验方案中：方案 A 试图防止 PICM，方案 B 试图逆转 PICM。在协议 A 中，我们在 AV 节点消融后注射了表达 TBX18（或报告构建体绿色荧光蛋白）的腺病毒载体，并观察了动物 8 周。在协议 B 中，PICM 是通过使用 AV 结消融和 4 周电子 RV 起搏建立的，此时 TBX18 被注射到希氏束区域。结果在方案 A 中，TBX18 生物起搏导致卓越的变时支持（62.4 ± 3 次/分钟 vs. 50.4 ± 0.4 次/分钟；p = 0.01），备用起搏器利用率较低（45 ± 2.6% vs. 94.6 ± 1.4%； p = 0.001) 和更大的射血分数（58.5 ± 1.3% 对 46.7 ± 2%；p = 0.001）。在方案 B 中，两组均在完全 AV 阻滞后 4 周出现完全成熟的 RV PICM；随后的干预导致更高的平均心率（56 ± 2 次/分钟 vs. 50.1 ± 0.4 次/分钟；p = 0.05），备用起搏器使用率降低（53 ± 8.2% vs. 95 ± 1.6%；p = 0.003）， TBX18 注射动物与对照动物的射血分数更高（61.7 ± 1.3% 与 49 ± 1.6%；p = 0.0003）。