Myocardial Substrate Driven Mechanistic Insights Into Atrial Fibrillation

心肌基质驱动的心房颤动机制见解

• 批准号: 9324445
• 负责人: Ravi Ranjan
• 金额: $ 57.52万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-15 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9324445
• 关键词: Ablation; Acute; Address; Affect; Agreement; Animal Model; Animals; Area; Arrhythmia; Atrial Fibrillation; Automobile Driving; Burn injury; Catheters; Chronic; Cicatrix; Clinical; Complex; Computer Simulation; Control Groups; Development; Diffuse; Disease; Effectiveness; Electrodes; Empiricism; Environment; Evaluation; Extracellular Space; Fibrosis; Frequencies; Gadolinium; Goals; Health; Heart; Heart Atrium; Human; Image; Image Analysis; Imaging Techniques; Incidence; Knowledge; Lead; Learning; Life; Magnetic Resonance Imaging; Maps; Measures; Modeling; Morbidity - disease rate; Myocardial; Myocardium; Nature; Outcome; Pathology; Patient Selection; Patients; Pharmacotherapy; Play; Positioning Attribute; Procedures; Process; Pulmonary veins; Radiofrequency Interstitial Ablation; Recurrence; Reporting; Risk; Role; Signal Transduction; Site; Staging; Stroke; Techniques; Testing; Time; Tissues; Universities; Utah; Ventricular Remodeling; base; contrast imaging; cost; density; economic cost; experience; gadolinium oxide; human subject; image processing; imaging biomarker; improved; insight; mortality; novel; simulation; success

 DESCRIPTION (provided by applicant): Atrial fibrillation (AF) affects 3-5 million people in the US alone. Although catheter-based radiofrequency ablation is routinely used today in treating AF, the high recurrence rate of up to 60 % continues to be a challenge. Over the years it has been shown that the atrial myocardium undergoes significant remodeling including fibrosis and this substrate is thought to play a major role in sustaining atrial fibrillation. Yet, the goal formost ablation procedures is to electrically isolate the pulmonary veins and this anatomical approach is based on the assumption that the pulmonary veins are the foci for ectopic activity driving atria fibrillation. More mechanistic approaches based on targeting "diseased" areas beyond the pulmonary veins have yielded varying results. This is mostly because there is no good way to identify these diseased areas. More recently, there have been some reports of rotors driving the AF. These rotors are based on high- density atrial electrical mapping. Targeting these rotors has shown some promising early results. The structural basis of these rotors and its anchor sites are still unknown. At the University of Utah we have pioneered using MRI to detect atrial wall remodeling in atrial fibrillation. Most of the MRI used for this purpose has been a gadolinium contrast imaging technique, which is good at detecting focal scar areas but not as good for detecting diffuse remodeling commonly seen in AF. To overcome this, a T1 based MRI mapping technique has been developed to quantify the extracellular space in the myocardium as a measure of the degree of atrial remodeling. We have also developed a chronic rapidly atrial paced large animal model of persistent atrial fibrillation. We hypothesize that developing a more mechanistic approach to ablation that includes the structural remodeling information of the atrial wall along with high density electrical mapping will lead to significant improvement in ablation outcomes. Based on serial high density electrical recording of electrograms processed in both time and frequency domains and MRI done at different time points in the progression of AF we will develop a detailed mechanistic understanding of AF. With the incorporation of structural remodeling information we will have a much better understanding of the drivers and anchor sites of these rotors. The structural remodeling can also form the basis of ablation. To test this hypothesis, we will make use of unique experimental, clinical, and animal model facilities as well as the extensive expertise in MRI acquisition and image analysis available at University of Utah. The clinical consequence will be reduced number of repeat procedures that are currently done due to arrhythmia recurrence at a significant cost and risk to patients.

 描述（由申请人提供）：仅在美国，房颤（AF）就影响了300万至500万人。尽管基于导管的射频消融目前已常规用于治疗房颤，但高达60%的高复发率仍然是一个挑战。多年来，已经表明心房心肌经历显著的重构，包括纤维化，并且认为这种基质在维持心房颤动中起主要作用。然而，大多数消融手术的目标是电隔离肺静脉，并且这种解剖方法基于肺静脉是驱动房颤的异位活动的病灶的假设。基于靶向肺静脉以外的“患病”区域的更多机械方法产生了不同的结果。这主要是因为没有好的方法来识别这些患病区域。最近，有一些关于转子驱动AF的报道。这些转子基于高密度心房电标测。以这些转子为目标已经显示出一些有希望的早期结果。这些转子的结构基础及其锚点仍然未知。在犹他州大学，我们率先使用MRI检测房颤患者的心房壁重构。大多数用于此目的的MRI一直是钆对比成像技术，这是很好的检测局灶性疤痕区域，但不好检测弥漫性重构常见于AF。为了克服这一点，基于T1的MRI映射技术已被开发来量化心肌细胞外空间作为衡量心房重构的程度。我们还开发了持续性房颤的慢性快速心房起搏大型动物模型。我们假设，开发一种更机械的消融方法，包括心房壁的结构重构信息沿着高密度电标测，将导致消融结局的显著改善。基于连续高密度电记录的电描记图处理在时域和频域和MRI在不同的时间点完成的AF的进展，我们将开发一个详细的机械理解AF。与结构重塑信息的结合，我们将有一个更好的了解这些转子的驱动程序和锚网站。结构重塑也可以形成消融的基础。为了验证这一假设，我们将利用独特的实验、临床和动物模型设施，以及犹他州大学在MRI采集和图像分析方面的广泛专业知识。临床结果将减少目前因心律失常复发而进行的重复手术次数，对患者造成巨大成本和风险。