左心房/肺静脉重构在孤立性心房颤动进展中的作用

目的 探讨孤立性心房颤动（房颤）进展过程中左心房/肺静脉重构的作用.方法 连续47例孤立性房颤患者在房颤心律下接受左心房/肺静脉CT检查,其中25例为阵发性房颤,22例为新发持续性房颤.通过对两组间有差异的CT指标进行Logistic回归分析,确定孤立性房颤进展的预测指标.结果 新发持续性房颤组的平均房颤持续时间为1～12（6.4±4.3）周.与阵发性房颤组比较,新发持续性房颤组呈现如下的左心房/肺静脉重构特征：（1）左心房非对称扩张;（2）左心房容积显著增大;（3）肺静脉开口扩张.经Logistic回归分析,左心房容积（P=0.003,OR=1.139,95%可信区间：1.046～1.240）是预测孤立性房颤进展最强的独立指标.左心房容积≥108 ml预测孤立性房颤由阵发性进展为持续性的敏感性为68.2%,特异性为88%.结论 孤立性房颤在由阵发性进展为持续性的过程中伴随有显著的左心房和肺静脉重构;左心房容积显著增加是该过程的独立预测指标.     

Morphological remodeling in atrial fibrillation

In the recent years, a tremendous amount has been learned about the pathophysiology of atrial fibrillation (AF). AF induces electrophysiological changes in the atria causing a perpetuation of the arrhythmia ("electrical remodeling"). Besides such AF-induced electrophysiological changes, which involve the downregulation of L-type calcium channels and thereby the calcium inward current, AF induces structural and ultrastructural changes in atrial tissue ("structural remodeling"). Calcium-dependent tissue alterations are induced by proteases and phosphatases like calpain and calcineurin. Furthermore, cardiac diseases like hypertension, heart failure, etc. activate the atrial angiotensin II system, and thereby, a progressive pro-arrhythmogenic atrial fibrosis is induced. Besides first clinical trials assessing the antiarrhythmic effects of angiotensin II receptor blockers in patients with AF, experimental data suggest that viral gene transfer can be used to transform fibroblasts to electrically conducting cardiomyocytes. This highly interesting methodology may be helpful to restore electrical conduction in fibrotic cardiac tissue.     

Structural remodeling in atrial fibrillation

Atrial fibrillation occurs and maintains itself in the context of a morphologically and functionally altered atrial substrate that can be induced by stressors such as underlying diseases (cardiac or noncardiac) or aging. The resultant structural remodeling is a slow process that progressively affects myocytes and the myocardial interstitium, and takes place from as early as the first days of atrial tachyarrhythmia. The left atrium, and particularly its posterior wall, is the location where remodeling is concentrated to the greatest extent. The mechanisms that underlie the remodeling process in atrial fibrillation have not yet been completely elucidated, although experimental and clinical investigations have indicated a number of signaling systems, inflammation, oxidative stress, atrial stretching and ischemia as factors involved in the cascade of events that leads to atrial fibrillation. The aim of this Review is to provide a comprehensive overview of the morphological changes that characterize the fibrillating atrial myocardium at histological and ultrastructural levels, and the established and hypothetical pathogenetic mechanisms involved in structural remodeling. This article also highlights the emerging therapies being developed to prevent progression of atrial fibrillation.     

心房重构在房颤中的作用

房颤的发病机制非常复杂,与心房的重构(包括电学重构、解剖重构和自主神经系统重构)密切相关.房颤可诱导离子通道蛋白表达和(或)功能异常,进而反馈性地促进心房功能性折返基质的形成,发生电学重构;循环往复的电学重构造成心房基质的改变,失活的心房肌细胞被纤维组织替代,心房逐渐纤维化,出现解剖重构;与此同时,心房广泛的纤维化进一步阻碍电冲动的传导,反过来加重电学重构;自主神经系统重构可通过正向反馈环机制促进房颤的维持和复发.早期治疗心房重构可延迟甚至预防房颤的发生和发展.     

心房顿抑与房颤后心房重构

心房颤动(房颤)复律后左房机械功能异常,其后将房颤恢复窦性心律时出现一过性的左心房和左心耳机械功能的异常称为心房顿抑,发生率约为38%～80%.房颤持续时间越长,心房顿抑越严重、持续时间越长,更易形成心耳血栓及房颤复发.近年研究提示,造成心房顿抑的原因与房颤后的心房重构有关.房颤诱导心房发生重构包括电重构、结构重构及缝隙连接重构.缝隙连接重构与心房电重构、结构重构均有关联,参与房颤的发生与持续,可能是心房顿抑发生的原因之一.本文就心房顿抑及与房颤后心房重构的关系进行综述,并对未来的研究方向作一展望.     

心房颤动与心房重构的最新进展

心房颤动（房颤,AF）是引起心血管发病和死亡的重要原因.房颤是常见的由一系列心脏疾病引起心房重构的终点事件,其本身也能引起心房重构从而促进心律失常的发展[1].随着人们对心房重构的机制及其在房颤进展中作用的逐渐认识,对离子通道调控机制和作用靶点的研究也有了较深入的发展.本文将重点综述这方面的进展.     

心房结构重构与心房颤动

房颤是临床最常见的心律失常之一.Feinberg等[1]对全球4个主要人群的流行病学调查结果显示,房颤发生率随年龄的增加而增加.中国一项来源于29 079例30～85岁患者的房颤流行病学调查显示,房颤患病率为0.77％,标准化率为0.61％,年龄分组显示患病率有随年龄增加的趋势[2].随着人口老龄化的发展,房颤的患病率必将不断攀升.然而房颤的确切发病机制并不十分清楚,临床治疗效果仍不理想.因此,从房颤的发生及维持机制方面入手,寻找预防和治疗房颤的新方法、新手段势在必行.     

MMP-9 in atrial remodeling in patients with atrial fibrillation

IntroductionAtrial fibrillation (AF) is the most common arrhythmia and is associated with significant morbidity and mortality. The impact of matrix metalloproteinases (MMPs) on structural atrial remodeling and sustainment of AF in patients with persistent and permanent AF is unresolved.ObjectivesThe aim was to evaluate MMP-9 and its tissue inhibitor-1 (TIMP-1) as markers of atrial remodeling in patients with persistent AF (PAF) who underwent electrical cardioversion (ECV) and in patients with permanent AF (continuous AF, CAF).Patients and methodsPlasma levels of MMP-9 and TIMP-1, clinical findings, and echocardiographic parameters were evaluated in 39 patients with AF and in 14 controls with sinus rhythm.ResultsThe concentrations of MMP-9 were significantly higher in patients with PAF and CAF compared to controls. There was a significant increase of MMP-9 after ECV in the persistent AF group. The values of TIMP-1 were not significantly different between the groups. In patients with AF, MMP-9 levels were positively related to posterior wall thickness of the LV (r = 0.356, P = 0.049) and body mass index (r = 0.367, P = 0.046).ConclusionElevated levels of MMP-9 were related to the occurrence and maintenance of AF. This suggests that MMP-9 can be a marker of atrial remodeling in patients with AF. Regulation of the extracellular collagen matrix might be a potential therapeutic target in AF.     

肾素-血管紧张素-醛固酮系统在心房颤动中对心房重构的影响

心房颤动（房颤）是临床上常见的与年龄增长密切相关的心律失常之一。如今，风湿性心脏病所致房颤的发病率已有所减少，但其他易感因素如高血压病、冠心病、心力衰竭等的发病率正不断增高，且房颤患者发生脑卒中的危险性也在增高…。对房颤机制的研究发现，心房重构即心房组织结构和电生理特性的变化，是这种心律失常发生发展的物质基础。[第一段]     

Molecular basis of electrical remodeling in atrial fibrillation

Atrial fibrillation (AF) is the most common cardiac arrhythmia, and is often associated with other cardiovascular disorders and diseases. AF can lead to thromboembolism, reduced left ventricular function and stroke, and, importantly, it is independently associated with increased mortality. AF is a progressive disease; numerous lines of evidence suggest that disease progression results from cumulative electrophysiological and structural remodeling of the atria. There is considerable interest in delineating the molecular mechanisms involved in the remodeling that occurs in the atria of patients with AF. Cellular electrophysiological studies have revealed marked reductions in the densities of the L-type voltage-gated Ca2+ current, I(Ca,L), the transient outward K+ current, I(TO), and the ultrarapid delayed rectifier K+ current, I(Kur), in atrial myocytes from patients in chronic AF. Similar (but not identical) changes in currents are evident in myocytes isolated from a canine model of AF and, in this case, the changes in currents are correlated with reduced expression of the underlying channel forming subunits. In both human and canine AF, the reduction in I(Ca,L) appears to be sufficient to explain the observed decreases in action potential duration and effective refractory period that are characteristic features of the remodeled atria. In addition, expression of the sarcoplasmic reticulum Ca2+ ATPase is reduced, suggesting that calcium cycling is affected in AF. These recent studies suggest that calcium overload and perturbations in calcium handling play prominent roles in AF-induced atrial remodeling. Although considerable progress has been made, further studies focused on defining the detailed structural, cellular and molecular changes that accompany the different stages of AF in humans, as well as in animal models of AF, are clearly warranted. It is anticipated that molecular insights gleaned from these studies will facilitate the development of improved therapeutic approaches to treat AF and to prevent the progression of the arrhythmia.     

Molecular mechanisms of remodeling in human atrial fibrillation

An important acknowledgement of the last several years is that atrial fibrillation (AF) modifies the electrical properties of the atrium in a way that promotes its occurrence and maintenance. This arrhythmogenic electrophysiological remodeling is well established, but can not explain by itself that 'AF begets AF'. This review describes molecular changes involving rapid functional alterations and slower changes in protein expression that cause electrical remodeling and contractile dysfunction in AF. An important molecular feature of AF is the reduction in L-type Ca(2+) channel function and protein expression. This reduction may serve to protect the cell against a potentially lethal Ca(2+) overload resulting from the increased activation rate in AF. Further, the review discusses the possible role of proteolytic systems, notably the calpains, as a mechanism linking Ca(2+) overload to reduced protein expression. Thus, it appears that the elaborate molecular changes in AF are directed primarily at protecting the myocyte from cellular stress. However, such early protection occurs at the expense of electrophysiological changes that promote the long-term maintenance of AF.     

非编码RNA与心房颤动结构重构的关系

心房结构重构是心房颤动(房颤)发生和赖以维持的关键环节.微小RNA、长链非编码RNA和环状RNA等非编码RNA在促进房颤心房结构重构中发挥重要作用.深入分析非编码RNA促进心房结构重构、导致房颤发生的病理生理机制具有重要临床意义,并可为寻找房颤防治新靶点提供理论依据.