Using Atrial Mechanics To Identify Fibrosis In Patients with Atrial Fibrillation

项目概要 心房颤动 (AF) 是一种非常流行的疾病，影响着 520 万美国人，每年造成 6-260 亿美元的损失 年，并增加心血管疾病、中风和死亡的风险。选择最佳治疗方案 每个 AF 患者仍然面临着日常的临床挑战，因为没有一种治疗方法在所有情况下都是最佳的。有症状的 患者最常接受药物治疗，或通过导管消融来隔离或破坏异常心房 组织。然而，两者通常都是无效的，并且没有一致的反应预测因子。 病理性心房纤维化是持续性房颤的主要原因，已多次被认为与其相关 发病机制并被提议作为个性化治疗的生物标志物。我们建议使用心脏 MRI (CMR) 基于力学的措施来识别局部心房纤维化。心房纤维化促进电生理学混乱 并且还会减弱局部心房力学，降低收缩力并增加僵硬度。对心房的影响 力学是很重要的。因此，我们假设减弱的心房力学提供了一种稳健的测量方法 心房纤维化。该项目的结果将是第一个经过组织学验证、可重现和可重复的结果 能够估计心房纤维化负担的临床工具。 这笔赠款的目的将利用心房纤维化和心房力学之间的机制联系来开发 并验证用于测量基于力学的纤维化分类器的临床工作流程。总体目标是 建立一种基于力学的、有区别的、经组织学验证的心房纤维化测量方法。的 为了实现这一目标，我们设计了以下目标。 目标 1. 稳健地测量窦性心律和 AF 中的 3D 心房 CMR 应变和硬度。心房运动 – 均匀 AF 期间 – 在 CMR 上很明显。我们的自由呼吸和心律失常不敏感的 CMR 协议使 测量心房力学，无需造影剂或超声心动图的限制，也无需辐射 CT 的。我们试图通过识别受损的心房力学来检测心房纤维化。 目标 2. 验证基于 CMR 力学的心房纤维化分类器并对其进行基准测试。最优指标为 从心房力学中识别局部心房纤维化尚不清楚。训练和验证分类器需要 基本事实，我们将使用组织学直接测量。然后将分类器进行基准测试 心房纤维化的常规标志物（电压测绘和 LGE-CMR）。 公共卫生意义 – 识别对特定治疗有反应的房颤 (AF) 患者 消融等策略是心脏病专家每天面临的挑战。为每个 AF 选择最佳治疗方法 患者仍然是一个开放的挑战。这项工作的结果将使临床医生能够更好地管理患有以下疾病的患者 通过使用基于心脏 MRI 的方法帮助识别心房纤维化负担来治疗心房颤动。

PROJECT SUMMARY Atrial fibrillation (AF) is a highly prevalent disease affecting 5.2 million Americans, costs the US $6-26 billion per year, and increases the risk of cardiovascular disease, stroke, and death. Selecting the optimal treatment for each AF patient remains a daily clinical challenge as no single treatment is best in all cases. Symptomatic patients are most frequently treated pharmacologically, or by catheter ablation to isolate or destroy aberrant atrial tissue. However, both are commonly ineffective and there are no consistent predictors of response. Pathological atrial fibrosis is a major contributor to sustaining AF, has repeatedly been implicated in its pathogenesis and is proposed as a biomarker for personalizing treatment. We propose to use cardiac MRI (CMR) mechanics-based measures to identify localized atrial fibrosis. Atrial fibrosis fosters chaotic electrophysiology and also attenuates local atrial mechanics, decreases contractility, and increases stiffness. The impact on atrial mechanics is substantial. Therefore, we hypothesize that attenuated atrial mechanics provide a robust measure of atrial fibrosis. The result of this project will be the first histologically validated, reproducible and repeatable clinical tool that enables estimation of atrial fibrosis burden. The aims of this grant will exploit the mechanistic link between atrial fibrosis and atrial mechanics to develop and validate a clinical workflow for measuring a mechanics-based classifier of fibrosis. The overall objective is to establish a mechanics-based and discriminatory measure of histologically validated atrial fibrosis. The following aims are designed to achieve this objective. AIM 1. To robustly measure 3D atrial CMR strain and stiffness in sinus rhythm and AF. Atrial motion – even during AF – is readily apparent on CMR. Our free-breathing and arrhythmia insensitive CMR protocol enables measuring atrial mechanics without the need for contrast or the limitations of echocardiography, nor the radiation of CT. We seek to detect atrial fibrosis by identifying impaired atrial mechanics. AIM 2. Validate and benchmark a CMR mechanics-based classifier of atrial fibrosis. The optimal index for identifying local atrial fibrosis from atrial mechanics is not known. Training and validating a classifier requires a ground truth, which we will measure directly using histology. The classifier will then be benchmarked against conventional markers of atrial fibrosis (voltage mapping and LGE-CMR). Public Health Significance – Identifying patients with atrial fibrillation (AF) that will respond to specific treatment strategies such as ablation is a daily challenge for cardiologists. Selecting the optimal treatment for each AF patient remains an open challenge. The results of this work will enable clinicians to better manage patients with atrial fibrillation by helping to identify the atrial fibrosis burden using cardiac MRI based methods.