心房肌建模与房颤消融的初步仿真研究
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摘要
心房颤动(简称房颤)是临床中最常见的心律失常疾病。房颤的特点是心房快速、不规则的活动,继而导致其失去机械收缩功能。随着年龄的增长,房颤的发病率不断上升,50多岁人群的发病率在0.5%,而80-90岁人群的发病率就上升到10%,最近几年,房颤的发病率呈日益增长的趋势。目前为止,虽然有很多关于房颤产生和维持机制的各种假说,如多子波折返假说、主导环折返假说和肺静脉异位局灶触发假说等,但房颤的确切机制仍不明确。
房颤的药物治疗主要有两种治疗策略：节律控制和心率控制。但多种药物治疗房颤的效果相对较低且有副作用和并发症,并不能长期维持窦性心律,很难达到预期的效果。
因此临床医生更多地追求确定的治疗方法,基于导管或外科手术消融的方法来治疗房颤,该方法是通过射频能量在心脏表面形成一些透壁消融线,通过去除导致房颤的潜在机制来治疗房颤。外科手术治愈房颤的同时,也提高了对房颤诱发和维持机制的认识,这在很大程度上也是导管消融技术发展的结果。
对于房颤患者的各种治疗方法常常以经验为依据,且需要临床研究和动物实验来评价方法的有效性。心脏建模仿真是研究房颤的有效方法之一,可以研究房颤的发生和维持的潜在机制,同时也可以评价房颤治疗方法的有效性。与临床研究和动物实验相比较,模型仿真的方法可以控制不同的实验条件,具有可重复性、可再现的优点。但现有心房模型在很多方面还有局限性,需要进一步完善。
本论文针对不同部位心房肌模型进行建模仿真研究,然后对房颤外科/射频导管消融方法进行仿真研究。主要研究内容有以下几个方面。
首先,对房颤基本概念、发生机制和主要治疗方法进行了回顾。
其次,基于犬心房肌的实验数据和前人发表的一些相关数据,首次建立了犬左心房肌和肌袖细胞模型。
第三,基于其他学者新近发表的人心房肌模型,仿真重现了正常人心房肌细胞的各离子流和动作电位曲线。在此基础上，通过改变相关的离子流参数,实现了不同部位人心房肌动作电位的仿真。
第四,基于Iyer和Gray发表的相位空间分布理论,提出了一种心脏折返模型中自动检测、跟踪相位奇异点的改进算法、比较分析了该算法的有效性和参数敏感精确性,并与Fenton和Karma提出的算法进行了比较。
最后,基于我们实验室构建的具有详细解剖结构的心房模型(3-D Cardiome-CN human heart model)上对8种临床上常用的术式(其中也包括了Cox-MazeⅢ术式)进行了仿真和评价,并提出了几种基于Cox-MazeⅢ的优化改进消融术式。
本论文的研究工作,对于今后进一步研究房颤的机制和房颤治疗方法具有重要意义。
Atrial fibrillation (AF) is the most common form of cardiac arrhythmia in clinical practice. AF is characterized by rapid and irregular activation of the atria, with consequence deterioration of atrial mechanical function. The occurrence of AF increases with age, with a prevalence rising from0.5%of people in their50s to nearly10%of the octogenarian population, and its incidence is increasing in the last few years. Despite different hypotheses are proposed such as multiple wavelet hypothesis, mother rotor hypothesis and focal triggers and drivers from the PVs etc., the exact mechanisms leading to perpetuation of AF are still undetermined so far.
There are two main pharmacological treatment strategies for patients with AF:rhythm control and rate control. Multiple pharmacological approaches have been tried to convert AF to sinus rhythm (SR). However, many of such drugs are relatively ineffective for maintaining sinus rhythm in the long term and are associated with significant side effects and complications.
Clinicians have therefore pursued more definitive treatment options, both catheter based and surgical, to treat patients with AF. Surgical/Radiofrequency (RF) catheter ablation is a therapeutic procedure that consists of creating lines of conduction block to interrupt AF. Surgical therapies designed to cure AF have developed in parallel with an improved understanding of the key pathophysiological concepts important in initiation and maintenance of AF, largely as a result of advances in catheter ablation technology.
The various treatments of AF remain largely based on empirical considerations and are usually evaluated in clinical study or in animal experiment. Heart modeling and simulation is one of the effective methods for AF research, it can be used to simulate AF and thus answer questions such as the mechanism involved in AF initiation or perpetration and the efficiency of therapy techniques. Compared to clinical and animal studies, an in silico approach has the advantages of repeatability and reproducibility under controlled conditions.
This thesis is focus on modeling of atrial cells with different areas and simulation study of the AF therapies:Surgical/Radiofrequency catheter ablation.
First, a brief review of the concepts and mechanisms of atrial fibrillation is presented, as well as a description of therapies aimed at AF including pharmacological treatments and non- pharmacological treatments.
Second, based on the RNC model, which is only specific to canine right atrial region, we developed models of left atrial myocytes and myocardial sleeves in PVs for the first time, based on our own experiment data and other published data.
Third, based on the published researches in recent years, ionic currents and action potential (AP) curves of normal human atrial myocytes are reproduced in our computer simulations. Then APs of human atrial myocytes with different anatomical regions of are simulated by changing ionic current parameters.
Fourth, based on the phase spatial distribution theory developed by Iyer and Gray, an automatic method is proposed to identify the phase singularity in cardiac reentry simulation, and the efficiency, accuracy and parameter sensitivity of the method are studied and compared with another commonly used method developed by Fenton and Karma.
Finally, based on3-D Cardiome-CN human heart model developed by our group,8different ablation patterns including the gold standard Cox-Maze Ⅲ are evaluated. Then several refined Cox-Maze Ⅲ ablation patterns are proposed.
The work of this thesis is very useful for further understanding the mechanisms underlying AF as well as refining AF therapeutic techniques.
房颤的药物治疗主要有两种治疗策略：节律控制和心率控制。但多种药物治疗房颤的效果相对较低且有副作用和并发症,并不能长期维持窦性心律,很难达到预期的效果。
因此临床医生更多地追求确定的治疗方法,基于导管或外科手术消融的方法来治疗房颤,该方法是通过射频能量在心脏表面形成一些透壁消融线,通过去除导致房颤的潜在机制来治疗房颤。外科手术治愈房颤的同时,也提高了对房颤诱发和维持机制的认识,这在很大程度上也是导管消融技术发展的结果。
对于房颤患者的各种治疗方法常常以经验为依据,且需要临床研究和动物实验来评价方法的有效性。心脏建模仿真是研究房颤的有效方法之一,可以研究房颤的发生和维持的潜在机制,同时也可以评价房颤治疗方法的有效性。与临床研究和动物实验相比较,模型仿真的方法可以控制不同的实验条件,具有可重复性、可再现的优点。但现有心房模型在很多方面还有局限性,需要进一步完善。
本论文针对不同部位心房肌模型进行建模仿真研究,然后对房颤外科/射频导管消融方法进行仿真研究。主要研究内容有以下几个方面。
首先,对房颤基本概念、发生机制和主要治疗方法进行了回顾。
其次,基于犬心房肌的实验数据和前人发表的一些相关数据,首次建立了犬左心房肌和肌袖细胞模型。
第三,基于其他学者新近发表的人心房肌模型,仿真重现了正常人心房肌细胞的各离子流和动作电位曲线。在此基础上，通过改变相关的离子流参数,实现了不同部位人心房肌动作电位的仿真。
第四,基于Iyer和Gray发表的相位空间分布理论,提出了一种心脏折返模型中自动检测、跟踪相位奇异点的改进算法、比较分析了该算法的有效性和参数敏感精确性,并与Fenton和Karma提出的算法进行了比较。
最后,基于我们实验室构建的具有详细解剖结构的心房模型(3-D Cardiome-CN human heart model)上对8种临床上常用的术式(其中也包括了Cox-MazeⅢ术式)进行了仿真和评价,并提出了几种基于Cox-MazeⅢ的优化改进消融术式。
本论文的研究工作,对于今后进一步研究房颤的机制和房颤治疗方法具有重要意义。
Atrial fibrillation (AF) is the most common form of cardiac arrhythmia in clinical practice. AF is characterized by rapid and irregular activation of the atria, with consequence deterioration of atrial mechanical function. The occurrence of AF increases with age, with a prevalence rising from0.5%of people in their50s to nearly10%of the octogenarian population, and its incidence is increasing in the last few years. Despite different hypotheses are proposed such as multiple wavelet hypothesis, mother rotor hypothesis and focal triggers and drivers from the PVs etc., the exact mechanisms leading to perpetuation of AF are still undetermined so far.
There are two main pharmacological treatment strategies for patients with AF:rhythm control and rate control. Multiple pharmacological approaches have been tried to convert AF to sinus rhythm (SR). However, many of such drugs are relatively ineffective for maintaining sinus rhythm in the long term and are associated with significant side effects and complications.
Clinicians have therefore pursued more definitive treatment options, both catheter based and surgical, to treat patients with AF. Surgical/Radiofrequency (RF) catheter ablation is a therapeutic procedure that consists of creating lines of conduction block to interrupt AF. Surgical therapies designed to cure AF have developed in parallel with an improved understanding of the key pathophysiological concepts important in initiation and maintenance of AF, largely as a result of advances in catheter ablation technology.
The various treatments of AF remain largely based on empirical considerations and are usually evaluated in clinical study or in animal experiment. Heart modeling and simulation is one of the effective methods for AF research, it can be used to simulate AF and thus answer questions such as the mechanism involved in AF initiation or perpetration and the efficiency of therapy techniques. Compared to clinical and animal studies, an in silico approach has the advantages of repeatability and reproducibility under controlled conditions.
This thesis is focus on modeling of atrial cells with different areas and simulation study of the AF therapies:Surgical/Radiofrequency catheter ablation.
First, a brief review of the concepts and mechanisms of atrial fibrillation is presented, as well as a description of therapies aimed at AF including pharmacological treatments and non- pharmacological treatments.
Second, based on the RNC model, which is only specific to canine right atrial region, we developed models of left atrial myocytes and myocardial sleeves in PVs for the first time, based on our own experiment data and other published data.
Third, based on the published researches in recent years, ionic currents and action potential (AP) curves of normal human atrial myocytes are reproduced in our computer simulations. Then APs of human atrial myocytes with different anatomical regions of are simulated by changing ionic current parameters.
Fourth, based on the phase spatial distribution theory developed by Iyer and Gray, an automatic method is proposed to identify the phase singularity in cardiac reentry simulation, and the efficiency, accuracy and parameter sensitivity of the method are studied and compared with another commonly used method developed by Fenton and Karma.
Finally, based on3-D Cardiome-CN human heart model developed by our group,8different ablation patterns including the gold standard Cox-Maze Ⅲ are evaluated. Then several refined Cox-Maze Ⅲ ablation patterns are proposed.
The work of this thesis is very useful for further understanding the mechanisms underlying AF as well as refining AF therapeutic techniques.
引文
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