MRI of Diffuse Left Ventricular Fibrosis in Atrial Fibrillation

项目摘要/摘要：房颤（AF）是一个重要的公共卫生问题，由于其高患病率 （超过200万美国人）。AF是一种多方面的进行性疾病， 增加死亡、中风和心力衰竭（HF）的风险。30-40%的AF患者发生HF， 对结果的影响-尽管有最佳的药物治疗，5年死亡率仍为25%。直接响应于 这些发人深省的统计数据，我们的建议促进了房颤管理的新模式-积极的节奏 控制可逆性左心室功能不全（LVD）患者，以改善LV功能和生存率。我们 关注房颤导管消融的理由是基于几项随机试验，这些试验报告称， 比抗心律失常药物更有效地恢复窦性心律，副作用更少。为临床 在AF患者的AF诱导LVD决策中，可逆性和不可逆性LVD之间的区别是 重要的是预测哪些患者在导管消融术后将经历改善的LV功能和存活。 我们的建议旨在开发一种新的MRI方法来区分可逆和不可逆的LVD， 房颤患者。在各种影像学生物标志物中，心脏纤维化作为不良结构性心脏病的标志物， 重塑，对于预测结果特别有用。MRI是唯一一种非侵入性检查， 使用心脏T1映射脉冲序列定量弥漫性心脏纤维化。然而，标准心脏T1 标测对于AF患者的成像有两个主要限制：对心律失常的敏感性和长扫描时间。在 针对这些局限性，我们将开发一种对心率不敏感的快速（AIR）心脏T1标测脉冲 顺序我们的中心假设是恢复窦性心律后左室功能恢复的程度 与既存弥漫性LV纤维化负荷呈负相关，可准确定量， 精确地使用AIR心脏T1标测脉冲序列。这一假设得到了我们令人信服的支持。 来自已建立的慢性AF犬模型的初步数据表明，AF诱导HF和弥漫性 尽管有药物控制率，但左心室纤维化;以及来自既往临床研究的令人信服的证据， 报道，AF消融术在药物心率控制下改善了HF患者的LV射血分数。的 我们建议的具体目标是开发和评估AIR心脏T1标测脉冲序列 (aim 1），评价MRI和弥漫性LV纤维化负荷的组织学测量之间的相关性， 建立AF诱导LVD的犬模型（目的2），并评估预先存在的LV纤维化对 预测患者导管消融后的LV功能恢复（目的3）。我们的长期目标是 建议建立一个风险分层系统，用于预测导管消融术后左室功能改善 无症状LVD患者的AF。通过使用风险分层方法进行房颤消融，我们的建议 促进了房颤管理的新模式：可逆性LVD患者的积极节律控制， 这将可能具有最高的成功机会并提高该患者群体的存活率。

Project Summary/Abstract: Atrial fibrillation (AF) is a significant public health issue due to its high prevalence (> 2 million Americans) in the general population. AF is a multi-faceted, progressive disease which can increase the risk of death, stroke, and heart failure (HF). HF occurs in 30-40% of AF patients and has major implications for outcome - 25% 5-year mortality rate despite optimal medical therapy. In direct response to these sobering statistics, our proposal promotes a new paradigm for AF management - an aggressive rhythm control in patients with reversible left ventricular dysfunction (LVD) to improve LV function and survival. Our rationale for focusing on catheter ablation of AF is based on several randomized trials, which reported that it restores sinus rhythm more effectively than anti-arrhythmic drugs and with fewer side effects. For clinical decision making in AF patients with AF-induced LVD, the distinction between reversible and irreversible LVD is important to predict which patients will experience improved LV function and survival after catheter ablation. Our proposal seeks to develop a novel MRI method to distinguish between reversible and irreversible LVD in AF patients. Among various imaging biomarkers, cardiac fibrosis, as a marker of adverse structural remodeling, is particularly useful for predicting the outcome. MRI is the only non-invasive test capable of quantifying diffuse cardiac fibrosis using a cardiac T1 mapping pulse sequence. However, standard cardiac T1 mapping has two major limitations for imaging patients in AF: sensitivity to arrhythmia and long scan time. In response to these limitations, we will develop an arrhythmia-insensitive rapid (AIR) cardiac T1 mapping pulse sequence. Our central hypothesis is that the degree of LV functional recovery after restoring sinus rhythm inversely correlates with pre-existing diffuse LV fibrosis burden, which can be quantified accurately and precisely using an AIR cardiac T1 mapping pulse sequence. This hypothesis is supported by our compelling preliminary data from an established canine model with chronic AF which show that AF induces HF and diffuse LV fibrosis despite pharmacologic rate control; and compelling evidence from a previous clinical study which reported that AF ablation improves LV ejection fraction in HF patients under pharmacologic rate control. The specific objectives of our proposal are to develop and evaluate an AIR cardiac T1 mapping pulse sequence (aim 1), evaluate the correlation between MRI and histological measurements of diffuse LV fibrosis burden in established canine models with AF-induced LVD (aim 2), and evaluate the value of pre-existing LV fibrosis for predicting the LV functional recovery following catheter ablation in patients (aim 3). The long-term goal of our proposal is to create a risk stratification system for predicting LV functional improvement after catheter ablation of AF in patients with asymptomatic LVD. By using a risk-stratified approach to AF ablation, our proposal promotes a new paradigm for AF management: an aggressive rhythm control in patients with reversible LVD, which will likely have the highest chance for success and improve survival in this patient population.