Neurocognition and Greater Maintenance of Sinus Rhythm in AF (NOGGIN AF)

心房颤动（AF）是最常见的持续性心律失常，影响1%-3%的一般 在老年人中的流行率更高（8%-10%）。AF与以下风险增加相关： 认知能力下降、痴呆、中风、心肌梗死、心力衰竭、慢性肾病和死亡率， 导致AF在美国每年的增量成本为260亿美元。房颤和认知能力下降有几个共同的风险 因素包括年龄增长和合并症，如高血压、糖尿病和心力衰竭。 抗凝引起的微出血、促炎和血栓形成前状态以及脑灌注不足可 累积导致无症状性脑梗死、白色物质高信号、脑萎缩和 功能性网络连接，也导致AF相关的认知功能下降。虽然AF和 发展的认知障碍已经建立，驱动机制和影响窦 节奏恢复尚未完全了解。 我们的长期目标是了解心律和神经健康之间的相互作用， 研究预防AF引起的认知功能障碍的方法。因此，在拟议的研究中，我们将测试我们的 假设在接受口服抗凝剂的房颤患者中， 消融术与药物治疗相比，由于大脑功能改善，长期神经损伤和功能障碍较少 血流和降低额外缺血性损伤的风险。我们的前瞻性，观察性的主要目标 临床试验是1）比较AF患者中阿尔茨海默病风险区域的结构皮质特征 导管消融与药物治疗; 2）比较导管治疗AF患者的脑血流量 消融与药物治疗; 3）比较导管消融与药物治疗AF患者的认知功能 治疗;和4）评估神经学结果与血浆和成像生物标志物之间的关系， 凝血和炎症。这将是第一项纳入全面神经认知测试的研究 成套检查、结构和功能神经成像、脑血流评估以及血浆和成像 生物标志物，以a）更好地描述每个已知的风险因素对认知障碍发展的贡献， 房颤患者的心率下降，以及B）评估使用导管消融术与药物治疗相比如何恢复窦性心律 可能会改变认知能力下降和痴呆症发展的轨迹。我们的初步数据显示， 6周或1年后，导管消融术未使认知功能或白色高信号负荷恶化， 而药物治疗的患者在1年时显示出与以下相关的大脑区域的皮质变薄更大 老年痴呆症，这种变薄与更差的认知能力有关。因此，这项研究意义重大， 将通过彻底改变我们对机制的理解来垂直推进AF管理领域， 房颤导致认知能力下降，并通过提供一个重要和必要的步骤， 通过导管消融控制，作为阻止导致认知障碍和痴呆的过程的策略。

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, affecting 1%-3% of the general population, with greater prevalence in older persons (8%-10%). AF is associated with an increased risk for cognitive decline, dementia, stroke, myocardial infarction, heart failure, chronic kidney disease, and mortality, resulting in an incremental yearly cost of AF in the US of $26 billion. AF and cognitive decline share several risk factors including advancing age and comorbidities such as hypertension, diabetes mellitus, and heart failure. Microbleeds from anticoagulation, a proinflammatory and prothrombotic state, and cerebral hypoperfusion can cumulatively result in silent cerebral infarction, white matter hyperintensities, brain atrophy, and disruption of functional network connectivity, and also lead to AF-related cognitive decline. While the link between AF and the development of cognitive impairment has been established, the driving mechanisms and the effect of sinus rhythm restoration are not completely understood. Our long-term goals are to understand the interaction between heart rhythm and neurologic health, and to investigate methods to prevent cognitive dysfunction due to AF. Thus, in the proposed study, we will test our hypothesis that among AF patients receiving oral anticoagulation, restoration of sinus rhythm with catheter ablation vs drug therapy leads to less long-term neurologic damage and dysfunction due to improved cerebral blood flow and lower risk for additional ischemic injury. The primary aims of our prospective, observational clinical trial are to 1) compare structural cortical characteristics in Alzheimer’s disease-risk regions in AF patients treated with catheter ablation vs drug therapy; 2) compare cerebral blood flow in AF patients treated with catheter ablation vs drug therapy; 3) compare cognitive function in AF patients treated with catheter ablation vs drug therapy; and 4) assess the relationship between neurologic outcomes and plasma and imaging biomarkers of coagulation and inflammation. This will be the first study to incorporate a comprehensive neurocognitive test battery, structural and functional neuroimaging, cerebral blood flow assessment, and plasma and imaging biomarkers to a) better delineate the contribution of each of the known risk factors to the development of cognitive decline in patients with AF, and b) assess how restoration of sinus rhythm using catheter ablation vs drug therapy may alter the trajectory of cognitive decline and development of dementia. Our preliminary data showed that catheter ablation did not worsen cognitive function or white matter hyperintensity burden 6 weeks or 1 year later, while drug therapy patients showed greater cortical thinning at 1 year in brain regions associated with Alzheimer’s, and this thinning correlated with worse cognitive performance. Thus, this study is significant, and will vertically advance the field of AF management by revolutionizing our understanding of the mechanisms by which AF induces cognitive decline, and by providing an important and necessary step toward justifying rhythm control by catheter ablation as a strategy to arrest the processes that lead to cognitive impairment and dementia.