摘要
背景 心房颤动（房颤）的发生和调控机制不清,药物和导管消融是主要治疗方法.国外研究证实导管消融优于药物治疗,但我国缺乏前瞻性、大样本的临床研究.房颤发生机制和干预方法学研究旨在探讨房颤发生和调控机制,并对其治疗方法学进行评估,包括两部分内容：①房颤的发生机制（SMAF）研究;②药物和导管消融治疗房颤的对比（CAPA）研究.基本原理 ①SMAF研究：房颤的发生和维持涉及电重构、结构重构和神经重构.SMAF研究通过基因工程技术筛选房颤相关基因,并建立相应基因修饰动物模型,探讨上游调控房颤的靶点与可行性.通过肾去交感神经术（RDN）改变心脏自主神经功能,研究其对房颤触发与维持的影响及机制;②CAPA研究：房颤患者使用抗心律失常药物维持窦性心律的安全性和有效性不理想.控制心室率的策略对患者生活质量及远期生存率也无明显益处.导管消融发展迅速,逐渐成为节律控制的重要手段.CAPA研究通过多中心、随机方案前瞻性研究两种治疗方法的优劣.设计方案 ①SMAF研究包括两个方面：一方面获取房颤患者心房肌组织,利用基因筛查技术寻找房颤相关基因,根据基因筛查结果,在房颤动物模型中验证,并构建相应的基因工程动物,开展电生理研究;另一方面建立急性和慢性房颤模型,观察RDN对房颤电重构、结构重构、神经重构等的影响及机制;②CAPA研究包括两个部分,分别针对阵发性房颤和持续性房颤,各入选600例患者,均分成药物治疗组和导管消融组.药物治疗组采取控制心室率或节律控制策略.导管消融规定主要术式及消融终点.随访3年,一级复合终点包括脑卒中、外周血管栓塞事件、大出血、恶性心律失常（快速心房率导致血流动力学障碍、室性心动过速、心室颤动）、因心力衰竭住院等;二级终点为心血管事件死亡率和总死亡率.结论 通过SMAF和CAPA研究,在机制研究中旨在探寻房颤上游调控的关键环节及调控手段,为房颤治疗提供新思路和新策略;在治疗研究中旨在观察两种治疗方法的终点和结果,为临床诊疗提供适合我国的循证医学依据,也为制定房颤管理指南和医疗行政管理策略提供依据.
Background Mechanism of atrial fibrillation （AF） is still unclear,its related genes and upstream regulatory mechanisms should be studied.The major treatments of AF include pharmacological therapy （PT） and catheter ablation （CA）,and it has been proved that CA is more suitable than PT,but our own clinical data remain unknown.The purpose of SMAF-CAPT is to explore the mechanism of AF and its suitable treatments strategy.The study consists of two parts：①study of mechanism of atrial fibrillation （SMAF）,②comparison of ablation and pharmacological therapy （CAPA）.Rationale ①SMAF study：Cardiac electrophysiology can be upstream regulated in many aspects and links,such as neurotransmitters,protein kinases,G proteins,the relation between them and arrhythmia has been increasingly taken seriously.Our previous studies have demonstrated that regulator of G protein signaling 5 （RGS5） is closely related by cardiac hypertrophy and arrhythmias.Furthermore,it also finds that micro RNA （miRNA） is closely associated with arrhythmia,which provides a new direction for upstream regulation of arrhythmia.In recent years,it has been proved patients with refractory hypertension can get benefits from renal sympathetic denervation （RDN）,which can change the autonomic nervous system and thus may affect the occurrence and maintenance of AF.However,the exact effect and mechanism are unclear,and the influence to RDN on atrium matrix remodeling also needs attention.Screen AF-related genes by genetic engineering technique,and then establish animals models of specific genes modification,SMAF aims to explore the feasibility and targets of upstream regulation to AF.And to study the impact and mechanisms of RDN on trigger and maintenance of AF.②CAPA Study：Pharmacological treatment （PT） can partly maintain the sinus rhythm,or improve the symptoms of patients with chronic heart failure,but its long-term effects seem poor.The strategy of ventricular rate control has no significant benefit on the quality and long-term survival rate.Catheter ablation （CA）,which has developed rapidly and became the best means of rhythm control.CAPA aims to compare the pros and cons of both treatments by prospective study.Design ①SMAF includes two aspects,One is to get atrial tissue from patients with AF,and search AF-related genes by genetic screening technology.According to the results,we will validate and construct the corresponding transgenic animals.Then,to conduct electrophysiological studies.The other is to build the models of acute and chronic AF,and observe the conditions of occurrence and maintenance of AF before and after RDN.Then,explore the influence of RDN on electrical remodeling,structural remodeling,nerve remodeding,atrial matrix,and investigate the corresponding molecular mechanism.②CAPA also consists of two parts of paroxysmal AF and persistent AF.Six hundred patients （a total of 1 200 cases） will be included in each part,and divided into pharmacological treatment group （PTG） and catheter ablation group （CAG）.PTG can implement as long as physicians can use drugs as medical guide,and whether ventricular rate control or rhythm control strategy relies on the advice of physicians and the will of patients.Primary endpoints of the study includes stroke,peripheral vascular embolic events,bleeding,malignant arrhythmia （hemodynamic disorders resulted to rapid atrial rate,ventricular tachycardia,ventricular fibrillation）,hospitalization of heart failure and so on.The second endpoints are cardiovascular events and total mortality.Conclusion Write the result of upstream regulation and automatical nerve intervention,SMAF study will provide new ideas,methods,and scientific basis for prevention and treatment of AF.Based on our national data,CAPA study will illustrate the more advantageous strategy,and thus to provide the basis for the management systems in the national level.
出处
《中华心律失常学杂志》
2014年第3期162-167,共6页
Chinese Journal of Cardiac Arrhythmias
基金
国家科技支撑计划（201113AI11B12）
关键词
心房颤动
导管消融
药物治疗
上游调控
Atrial fibrillation
Catheter ablation
Pharmacological treatment
Upstream regulation
