左室心内膜起搏行心脏再同步治疗抑制失同步化缺血性心力衰竭促发心脏性猝死的电生理机制

Sudden cardiac death (SCD) is the major cause of chronic heat failure (HF). Cardiac resynchronization therapy has been approved to decrease the mortality of HF. However, conventional left ventricular epicardial pacing during CRT could increase the dispersion of ventricular repolarization and reverse the direction of activation conduction, and thus, has a potential risk of arrhythmogenesis and non-response which decreases the clinical efficacy of CRT.Our research team has established a canine moedel of chronic heart failure with left bundle branch block (LBBB),and developed a technology to perform simutaneous Bi-ventricular electrical mapping. The aims of this project are as follows. 1)Establish a model of HF which is commonly seen in the clinical setting;2)Compare the difference of electrical substrate including global bi-ventricular endocardial and left ventricular transmural dispersion of repolarization, activation conduction, and restitution properity between left ventricular endocardial and epicardial pacing during CRT; 3)Optimize CRT efficacy by adjusting left endocardial pacing sites based on electrophysiological substrate in the different ischemic areas. The project is performed to provide evidence for left endocardial pacing during CRT suppressing SCD in patients with HF.

心脏性猝死（SCD）是心力衰竭（HF）的主要死亡原因，心脏再同步治疗（CRT）可降低HF死亡率。但是，传统CRT的左室心外膜起搏可因增加心室复极离散度和逆转激动传导方向而存在致室性心律失常风险和无应答现象，从而降低CRT疗效。本研究组在建立左束支阻滞型HF模型和双心室同步电生理标测平台的基础上，本项目拟进一步研究：1）建立临床常见的CRT无应答HF模型，慢性缺血性心脏病致HF伴左束支阻滞模型；2）利用双心室同步标测技术，比较左室心内膜与心外膜起搏行CRT对双心室整体心内膜和左室跨心肌层复极离散度、激动传导特性和不应期整复性等电生理基质的作用和差异；3）以电生理基质为基础，优化CRT在不同缺血区域下的不同左室心内膜起搏部位。本项目可为左室心内膜起搏行CRT改善HF促发SCD的电生理基质及其主要作用途径提供重要线索，为提高CRT应答率，防治HF促发SCD提供实验依据，项目具有一定的转化意义。

心脏性猝死（SCD）是心力衰竭（HF）的主要死亡原因，心脏再同步治疗（CRT）可降低HF死亡率。但是，传统CRT的左室心外膜起搏可因增加心室复极离散度和逆转激动传导方向而存在致室性心律失常风险和无应答现象，从而降低CRT疗效。本项目在建立左束支阻滞型HF模型和双心室同步电生理标测平台的基础上，本项目主要研究内容：1）建立临床常见的CRT无应答HF模型，慢性缺血性心脏病致HF伴左束支阻滞模型；2）利用双心室同步标测技术，比较左室心内膜与心外膜起搏行CRT对双心室整体心内膜和左室跨心肌层复极离散度、激动传导特性和不应期整复性等电生理基质的作用和差异；3）以电生理基质为基础，优化CRT在不同左室心内膜起搏部位。主要研究成果：1）制作针状电极用于心内膜至心外膜跨心肌层标测和起搏，成功制作慢性失同步化缺血性心力衰竭模型；2）对于不应期离散度，左室相同部位起搏，心内膜起搏优于心外膜起搏；同时，对于左室心内膜起搏，心底部优于心尖部起搏；3）HF时室颤激动特征分析显示，室颤维持3分钟内，左右室室颤的激动频率梯度持续存在；4）通过本项研究，累计发表论文5篇，培养研究生3名。本项目为左室心内膜起搏行CRT改善HF促发SCD的电生理基质及其主要作用途径提供重要线索，为提高CRT应答率，防治HF促发SCD提供实验依据，项目具有一定的转化意义。