Electrophysiological, Electroanatomical, and Structural Remodeling of the Atria as Consequences of Sustained Obesity
Electrophysiological, Electroanatomical, and Structural Remodeling of the Atria as Consequences of Sustained Obesity
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DOI：
10.1016/j.jacc.2015.04.058
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发表时间：
2015-07-07
影响因子：
24
通讯作者：
Sanders, Prashanthan
中科院分区：
文献类型：
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作者：
Mahajan, Rajiv;Lau, Dennis H.;Sanders, Prashanthan
背景 肥胖和心房颤动 (AF) 是具有重大后果的公共卫生问题。 目的 本研究旨在描述持续性肥胖中 AF 的全球电生理和结构底物的发展。 方法 10 只羊随意饲喂高热量饮食以诱导肥胖超过 36 周，并在这种状态下再维持 36 周； 10只严格控制体重的瘦羊作为对照。所有绵羊均接受了电生理和电解剖测绘；血流动力学和影像学评估（超声心动图和双能 X 射线吸收测定法）；以及组织学和分子评估。评估包括心房电压、传导速度 (CV) 和不应性（7 个部位，2 个周期长度）、房颤易感性、脂肪浸润、心房纤维化和心房转化生长因子 (TGF)-β 1 表达。 结果与年龄匹配的对照相比，长期肥胖的绵羊表现出更高的全身脂肪 (p < 0.001)； LA 体积 (p < 0.001)； LA 压力 (p < 0.001) 和 PA 压力 (p < 0.001)；心房CV降低（LA p < 0.001），传导异质性增加（p < 0.001）；分数电图增加（p < 0.001）；后 LA 电压降低 (p < 0.001)，电压异质性增加 (p < 0.001)；有效不应期 (ERP) (p > 0.8) 或 ERP 异质性 (p > 0.3) 没有变化。肥胖与 AF 发作次数增多 (p = 0.02)、时间延长 (p = 0.01) 和累积持续时间较长 (p = 0.02) 相关。肥胖组心外膜脂肪浸润后 LA（p < 0.001），与该区域心内膜电压降低一致。肥胖组的心房纤维化 (p = 0.03) 和 TGF-β 1 蛋白 (p = 0.002) 增加。 结论 持续肥胖导致整体双心房心内膜重塑，其特征为 LA 扩大、传导异常、分段电图、促纤维化 TGF-β 1 表达增加、间质性心房纤维化和 AF 倾向增加。肥胖与左心后心内膜电压降低和心外膜脂肪浸润邻近的左心后肌有关，这是房颤的独特基质。 (C) 2015 年，美国心脏病学会基金会。
BACKGROUND Obesity and atrial fibrillation (AF) are public health issues with significant consequences.OBJECTIVES This study sought to delineate the development of global electrophysiological and structural substrate for AF in sustained obesity.METHODS Ten sheep fed ad libitum calorie-dense diet to induce obesity over 36 weeks were maintained in this state for another 36 weeks; 10 lean sheep with carefully controlled weight served as controls. All sheep underwent electrophysiological and electroanatomic mapping; hemodynamic and imaging assessment (echocardiography and dual-energy x-ray absorptiometry); and histology and molecular evaluation. Evaluation included atrial voltage, conduction velocity (CV), and refractoriness (7 sites, 2 cycle lengths), vulnerability for AF, fatty infiltration, atrial fibrosis, and atrial transforming growth factor (TGF)-beta 1 expression.RESULTS Compared with age-matched controls, chronically obese sheep demonstrated greater total body fat (p < 0.001); LA volume (p < 0.001); LA pressure (p < 0.001), and PA pressures (p < 0.001); reduced atrial CV (LA p < 0.001) with increased conduction heterogeneity (p < 0.001); increased fractionated electrograms (p < 0.001); decreased posterior LA voltage (p < 0.001) and increased voltage heterogeneity (p < 0.001); no change in the effective refractory period (ERP) (p > 0.8) or ERP heterogeneity (p > 0.3). Obesity was associated with more episodes (p = 0.02), prolongation (p = 0.01), and greater cumulative duration (p = 0.02) of AF. Epicardial fat infiltrated the posterior LA in the obese group (p < 0.001), consistent with reduced endocardial voltage in this region. Atrial fibrosis (p = 0.03) and TGF-beta 1 protein (p = 0.002) were increased in the obese group.CONCLUSIONS Sustained obesity results in global biatrial endocardial remodeling characterized by LA enlargement, conduction abnormalities, fractionated electrograms, increased profibrotic TGF-beta 1 expression, interstitial atrial fibrosis, and increased propensity for AF. Obesity was associated with reduced posterior LA endocardial voltage and infiltration of contiguous posterior LA muscle by epicardial fat, representing a unique substrate for AF. (C) 2015 by the American College of Cardiology Foundation.