基于门控心肌灌注显像对缺血性心肌病CRT应答的机制研究

Cardiac resynchronization therapy (CRT) has been shown to be an established treatment for heart failure, but unfortunately more than 50% of patients showed no-response to this therapy in ischemic cardiomyopathy without left bundle branch block (LBBB). The optimal selection of the left ventricular lead position may be an important target to improve the response to CRT for those patiens. Theoretically, it can maximize correct the left ventricular electrical dyssynchrony and mechanical dyssynchrony when the left ventricular lead implanted in the latest electrical activated site or the latest mechanical contracted site (Away from the scar of myocardium) for CRT, but actually the latest electrical activated site and the latest mechanical contracted site of left ventricular were inconsistent which confirmed by relevant studies and our preliminary experiment, meanwhile, it is not yet clear that in which site of left ventricular lead implanted can produce the best response to CRT. Based on the mechanism of correcting left ventricular mechanical contract dyssynchrony is important for response to CRT, we hypothesis that the curative effect of CRT may be better when left ventricular lead implant in the latest mechanical contracted site than in the latest electrical activated site. In our study, We will establish the model of ischemic cardiomyopathy without LBBB in pigs, and assess the latest mechanical contraction and the latest electrical activation of left ventricular respectively by gated myocardial perfusion imaging and three-dimensional anatomical mapping, to clarify the relationship between the latest mechanical contracted site and the latest electrical activated site in ischemic cardiomyopathy without LBBB, to reveal the optimal selection of the left ventricular lead position to give the best response to CRT, it can provide theoretical evidence and effective solution for response to CRT in ischemic cardiomyopathy without LBBB through our study.

心脏再同步化治疗（CRT）是心衰的有效治疗方法，但不伴左束支传导阻滞（LBBB）的缺血性心肌病CRT无应答比例高达50%。对此类患者明确左室电极最佳植入位置可能是提高CRT应答的重要靶点。理论上CRT左室电极植入于最晚电激动或最晚机械收缩部位（避开瘢痕心肌）可最大程度纠正左室电、机械收缩不同步，进而提高左心功能，但相关研究及预实验发现左室最晚电激动与最晚机械收缩部位不一致，CRT左室电极植入于哪个部位效果最佳尚不明确。基于纠正左室机械收缩不同步是CRT应答的重要机制，我们推测左室电极植入于最晚机械收缩部位时CRT疗效可能优于最晚电激动部位。我们拟用不伴LBBB的猪缺血性心肌病模型，应用门控心肌灌注显像和三维电解剖标测分别评估左室最晚机械收缩与最晚电激动部位，明确两者的关系，揭示左室电极分别植入于两者时CRT疗效哪个更优，为不伴LBBB的缺血性心肌病从CRT中获益提供理论依据和有效解决方案。

心脏再同步化治疗（CRT）是心衰的有效治疗方法，但不伴左束支传导阻滞（LBBB）的缺血性心肌病CRT无应答比例高达50%。对此类患者明确左室电极最佳植入位置可能是提高CRT应答的重要靶点。理论上CRT左室电极植入于最晚电激动或最晚机械收缩部位（避开瘢痕心肌）可最大程度纠正左室电、机械收缩不同步，进而提高左心功能，但相关研究及预实验发现左室最晚电激动与最晚机械收缩部位不一致，CRT左室电极植入于哪个部位效果最佳尚不明确。基于纠正左室机械收缩不同步是CRT应答的重要机制，本项目构建不伴LBBB的缺血性心肌病模型，于建模前和建模后均行静息GMPI及Carto三维电解剖标测，通过GMPI定量分析评估左室瘢痕心肌及左室机械收缩同步性，并得到避开瘢痕心肌的左室最晚机械收缩部位；应用Carto三维电解剖标测电压图评估瘢痕心肌，通过Carto电激动传导图评价左室电同步性，并根据左室电激动顺序得到避开瘢痕心肌的左室最晚电激动部位，探讨不伴LBBB的缺血性心肌病左室最晚机械收缩部位（避开瘢痕部位）与左室最晚电激动部位（避开瘢痕部位）的关系；揭示不伴LBBB的缺血性心肌病左室电极植入于左室最晚机械收缩部位时CRT疗效是否优于左室最晚电激动部位。结果发现：构建不伴LBBB的缺血性心肌病模型后，均出现了左室机械收缩不同步和左室电不同步，且左室最晚电激动部位和左室最晚机械收缩部位均位于瘢痕区，而非瘢痕区域的左室最晚电激动部位与最晚机械收缩部位并不完全吻合。当CRT左室电极植入于无创GMPI左室最晚收缩部位时，其LVEF值较起搏前明显增加，提示CRT应答，其LVEF的改善程度亦明显高于CRT左室电极位于左室最晚电激动部位、交界区和瘢痕区。通过本研究表明，无创GMPI评价左室最晚收缩部位可有效指导CRT左室电极植入，提高不伴LBBB的缺血性心肌病的CRT应答，明显优于有创 Carto评价左室最晚电激动部位。该研究为指导不伴LBBB的缺血性心肌病CRT提供新的理论依据，以无创核素心肌灌注显像GMPI评估左室最晚收缩部位代替有创Carto评价左室最晚电激动部位，进而避免不必要的有创诊疗，为不伴LBBB的缺血性心肌病从CRT中获益提供有效解决方案。