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

AF 中的神经认知和窦性心律的更好维持 (NOGGIN AF)

• 批准号: 10299458
• 负责人: Joseph P Mathew
• 金额: $ 74.01万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10299458
• 关键词: Ablation; Affect; Age; Alzheimer' s Disease; Alzheimer' s disease risk; Anti-Arrhythmia Agents; Anticoagulation; Arrhythmia; Atrial Fibrillation; Attention Concentration; Automobile Driving; Biological Markers; Blood Platelets; Blood Vessels; Brain; Brain Injuries; Brain region; Cardiac ablation; Cerebral Infarction; Cerebral Ischemia; Cerebrovascular Circulation; Characteristics; Chronic Kidney Failure; Clinical Trials; Coagulation Process; Cognitive; Data; Dementia; Development; Diabetes Mellitus; Disease; Early Intervention; Elderly; Endothelium; Enrollment; General Population; Goals; Health; Heart; Heart failure; Hypertension; Impaired cognition; Individual; Inflammation; Inflammatory; Lead; Link; Maintenance; Maps; Measures; Metabolic; Methods; Myocardial Infarction; National Heart, Lung, and Blood Institute; National Institute of Neurological Disorders and Stroke; Nervous System Trauma; Neurocognition; Neurologic; Neurologic Dysfunctions; Neurological outcome; Oral; Pathologic; Patients; Pharmaceutical Preparations; Pharmacotherapy; Pilot Projects; Plasma; Prevalence; Procedures; Process; Reporting; Research; Risk; Risk Factors; Signal Transduction; Sinus; Stroke; Structure; Techniques; Testing; Therapeutic Embolization; Thick; Thinness; Thrombin; Tissues; Tube; White Matter Hyperintensity; brain dysfunction; brain health; cerebral atrophy; cerebral hypoperfusion; cerebrovascular; clinical practice; cognitive development; cognitive function; cognitive performance; comorbidity; cost; dementia risk; flexibility; gray matter; heart rhythm; imaging biomarker; improved; insight; ischemic injury; lifetime risk; minimally invasive; mortality; neurocognitive test; neuroimaging; neuroinflammation; older patient; preservation; prevent; prospective; restoration; sound; stroke risk; thrombotic; treatment optimization; vascular cognitive impairment and dementia

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.

心房颤动 (AF) 是最常见的持续性心律失常，影响一般人群的 1%-3% 人群中，房颤患病率在老年人中更高（8%-10%），与房颤风险增加相关。 认知能力下降、痴呆、中风、心肌梗塞、心力衰竭、慢性肾病和死亡， 导致美国每年因 AF 造成的费用增加 260 亿美元，而 AF 和认知能力下降也存在多种风险。 因素包括年龄增长和高血压、糖尿病和心力衰竭等合并症。 抗凝、促炎和促血栓状态以及脑灌注不足引起的微出血可以 累积起来会导致无症状的脑梗塞、白质高信号、脑萎缩和大脑功能紊乱。 功能性网络连接，也会导致与 AF 相关的认知能力下降。 认知障碍发展的驱动机制和窦性效应的影响已经确定 节律恢复尚未完全了解。 我们的长期目标是了解心律与神经系统健康之间的相互作用，并 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，我们将测试我们的方法。 假设 AF 患者经口接受抗凝治疗，通过导管恢复窦性心律 与药物治疗相比，消融治疗由于改善了大脑功能，可减少长期神经损伤和功能障碍。 血流量和降低额外缺血性损伤的风险是我们前瞻性观察的主要目标。 临床试验的目的是 1) 比较 AF 患者阿尔茨海默病风险区域的结构皮质特征 2）比较接受导管治疗的房颤患者的脑血流量 消融与药物治疗；3) 比较导管消融与药物治疗的 AF 患者的认知功能 治疗；4) 评估神经系统结果与血浆和影像生物标志物之间的关系 这将是第一项纳入综合神经认知测试的研究。 电池、结构和功能神经影像、脑血流评估以及血浆和成像 生物标志物 a) 更好地描述每个已知风险因素对认知发展的贡献 AF 患者的心率下降，b) 评估使用导管消融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。 6周或1年后，导管消融并未使认知功能或白质高信号负担恶化， 而药物治疗患者在 1 年时表现出与以下相关的大脑区域的皮质变薄程度更大： 阿尔茨海默病，这种稀疏与较差的认知能力相关，因此，这项研究很重要，而且。 将通过彻底改变我们对机制的理解来垂直推进房颤管理领域 房颤会导致认知能力下降，并为证明节律提供重要且必要的一步 通过导管消融作为阻止导致认知障碍和痴呆的过程的策略进行控制。