MRI of Diffuse Left Ventricular Fibrosis in Atrial Fibrillation

描述（由申请人提供）：房颤（AF）是一个重要的公共卫生问题，由于其在普通人群中的高患病率（约200万美国人）。房颤是一种多方面的进行性疾病，可增加死亡、中风和心力衰竭（HF）的风险。心衰发生率为30-40%的房颤患者，并对预后有重大影响——尽管采用最佳药物治疗，但仍有25%的5年死亡率。直接回应这些令人清醒的统计数据，我们的建议促进了房颤管理的新范式-对可逆性左心室功能障碍（LVD）患者进行积极的心律控制，以改善左室功能和生存率。我们关注房颤导管消融的基本原理是基于几项随机试验，这些试验报道它比抗心律失常药物更有效地恢复窦性心律，而且副作用更少。对于房颤合并房颤诱发的LVD患者的临床决策，区分可逆性和不可逆性LVD对于预测哪些患者在导管消融后左室功能改善和生存很重要。我们的建议旨在开发一种新的MRI方法来区分房颤患者的可逆性和不可逆性LVD。在各种成像生物标志物中，心脏纤维化作为不良结构重塑的标志物，对预测预后特别有用。MRI是唯一一种能够使用心脏T1脉冲序列定量弥漫性心脏纤维化的非侵入性测试。然而，标准的心脏T1制图对房颤患者的成像有两个主要限制：对心律失常的敏感性和扫描时间长。针对这些限制，我们将开发心律失常不敏感快速（AIR）心脏T1测绘脉冲序列。我们的中心假设是窦性心律恢复后左室功能恢复程度与

DESCRIPTION (provided by applicant): 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.