肺静脉前庭放射状线性消融治疗阵发性房颤的机制研究

Our randomized clinical trail has been selected in Late-breaking Clinical Trail in 2012 AHA scientific session,presented in the new insight of treatment for cardiovascular diseases,and published in Circulation AE. The results revealed that pulmonary antrum radial-linear ablation based on organized substrate modification of substract is a safe and effective strategy for ablation of paroxysmal atrial fibrillation. International scholars paid close attention to this report, suggesting the necessity and urgency of study for the mechanisms of the procedure. The proposal of this project is based on the 2012 HRS Expert Consensus Statement on ablation of atrial fibrillation. This study focus on the main substrates/mechanisms relative to atrial fibrillation, including multiple random propagating wavelets, autonomic nervous system, ligament of Marshall and focal trigger/complex fractionated atrial EGMs. This study will be carried on in vitro and in vivo animal hearts and patients with paroxysmal atrial fibrillation. With the aid of optical mapping system and 3D cardiac mapping system with grouping control and self control. The interventional effect of pulmonary antrum radial-linear ablation on above-mentioned substrates/mechanisms of atrial fibrillation will be investigated. The continuity of ablation line lesion and the endpoint of linear ablation will be confirmed by pathological study. This study is featured by from phenomenon to essence, against multipal mechanisms supposed to atrial fibrillation.This is the first study in human to confirm the hypothesis of multiple random propagating wavelets in Pulmonary antrum. The study will provide new insight into the mechanisms for the effectiveness of pulmonary antrum radial-linear ablation in atrial fibrillation.

我们完成的临床试验入选2012 AHA科学大会最新突破性研究，在主会场心血管病治疗新思维论坛报告及Circulation AE发表，揭示以有序基质改良为理念的肺静脉前庭放射状线性消融是一种有效的阵发性房颤根治策略。国际学者予以高度关注并指出了该术式有效性机制研究的必要性和迫切性。本课题依据2012 HRS房颤指南及本术式设计原理，对房颤的主要相关基质/机制:多重随机传导子波，自主神经，Marshall韧带及局灶触发/复杂碎裂电位等在动物离体和在体心脏以及房颤病人进行系列研究。借助光学标测系统和心脏三维标测系统，采用分组对照及自身前后对照的实验设计，探讨肺静脉前庭放射状线性消融对上述房颤基质/机制的干预作用。病理学验证消融线连续性及线性消融终点。课题特色在于从现象到本质、多机制并举及首次直接干预性验证房颤的肺静脉前庭多重随机传导子波机制，为房颤肺静脉前庭放射状线性消融术提供可靠的理论依据。

房颤肺静脉电隔离术（PVI）与肺静脉前庭放射状线性消融术（PAR）分别代表“堵”与“疏”的不同消融策略。PVI在于隔离而不损毁触发灶，PAR可干预房颤多子波折返等多种机制，本课题在PAR临床有效性基础上，进一步研究其对房颤的有效机制。提出了“以疏代堵”的消融理论，利用三维高密度标测技术，在房颤患者及实验动物，对房颤PAR消融的有效机制进行了广泛研究。此外，还将PAR消融技术应用于临床慢性房颤消融，通过2年的随访，证实了其良好的疗效。. 研究发现PAR消融组中73%在消融时出现迷走反射，PVI组为39%，提示PAR可以更多地消除自主神经支配。PAR应用于阵发性房颤研究，62例患者共发现113个触发灶，肺静脉口内外是触发灶的主要潜藏部位，PAR术与PVI相比，最大的优势是能够直接精准破坏这些触发灶，而不导致肺静脉狭窄，房颤消融即刻成功率100%。PAR应用于持续性房颤研究，采用PAR消融术与低电压区消融相结合的策略，35例病程少于12个月的持续性房颤，14例被PAR消融终止，术中房颤转房扑5例，均被消融终止；16例电除颤恢复窦律，继以低电压区消融。对133例阵发性房颤患者进行3年的随机临床试验长期随访研究发现，在单次术后36个月未服用抗心律失常药物的情况下，PAR消融组65%的患者及PVI组42%的患者无房颤复发。随访终点72小时Holter监测发现PAR消融组房颤负荷显著低于PVI组。以上实验结果均显示PAR消融术是一项简单、安全、有效的治疗房颤的消融策略。此外，本课题的实用新型专利轴支撑冷盐水灌注消融导管，获得国家科技支撑项目，动物实验证实与传统导管相比，新型导管在操控稳定性、定位准确性等方面均具优势。离体羊心脏灌流模型进行诱发性房颤实验还在方法学探索中。临床研究中，经费使用较少。. 课题共发表论著4篇，论文国际引用4次（欧洲心脏病学杂志等）。参加国际、国内会议交流8次，实用新型专利授权1项，国家“十二五”国家科技支撑计划1项，主编出版射频消融专著1部，获得嘉定区科技进步三等奖1项。研发轴支撑房颤消融导管1项，已申报中国CFDA产品注册证，并收到CFDA医疗器械技术评审中心医疗器械注册补充资料通知。毕业硕士生3名，在读临床博士生2名。多家科普网站多次介绍PAR消融术。