超声预测心房颤动导管消融术后复发的研究现状

吴晓宇 周根青 刘少稳

随着对心房颤动(简称房颤)发生机制认识的逐渐深入以及导管消融技术水平的不断进步，导管消融治疗房颤的新模式已被广泛运用于临床。导管消融在改善心悸症状、提高生活质量和减少房颤再发等方面均优于抗心律失常药物治疗[1]，但仍有38.9%的阵发性房颤和58.4%的非阵发性房颤患者在三年内出现房颤复发[2]。导管消融术后的高复发率成了临床工作中的一个难题，如何降低房颤患者导管消融术后的复发率是临床研究工作的重要部分。随着超声技术的发展，多种超声检测的特异性预测因子被用来评估房颤复发。笔者将围绕房颤导管消融术后复发的超声预测因子的研究现状进行综述。

1 超声预测消融术后房颤复发的理论基础

在山羊的房颤模型中发现，纤维化和心肌细胞肥大等心房的结构性重构是引起颤动波传导方式改变和房颤稳定性增加的潜在机制[3]。细胞外基质中胶原合成，包绕在心房肌纤维周围形成结缔组织间隔，引起心房纵向肌束电分离[4]。房颤又引起心脏功能障碍和电重构，这些改变与房颤互为因果并造成恶性循环[5]，心肌重构加重，房颤也趋于稳定，甚至能从阵发性房颤进展为持续性或永久性房颤[3]。消融术后肺静脉传导恢复、非肺静脉异位灶的存在是房颤复发的重要原因[6-8]，而消融引起的局部、全身炎症反应和自主神经功能改变是术后早期复发房颤的可能原因[9-10]。可见,术前的左房基质影响了术后房颤的复发，复发率与疾病本身的病理生理机制有关。通过超声检测房颤患者心房的结构和功能改变，就能帮助对消融术后房颤复发情况进行评估。

2 结构性预测因子

2.1术前左房直径(left atrial diameter, LAD) 正常的心肌在心力衰竭、心室壁增厚或心脏增大后更容易发生房颤等心律失常[5]。早期的几项研究检测房颤发生前后超声心动图上左房大小，发现左房增大是房颤发作的独立预测因子[11-13]。目前临床多采用胸骨旁心脏长轴观来测量术前LAD，这种方法因操作简便被广泛运用于评价左房的大小。Gerede等[14]在51例阵发性房颤患者的研究中发现，复发组术前LAD明显大于未复发组[( 41 ± 5 ) mm vs ( 34 ± 5 ) mm，P<0.000 1],并且界定术前LAD > 40 mm是房颤复发的预测因子。McCready等[15]发现，术前LAD < 43 mm是房颤消融术后房颤长期缓解的预测因子(敏感性92%，特异性52%)。Miyazaki等[16]对474例药物治疗无效的阵发性房颤患者进行了更加细致的分析,发现LAD每增加1mm，消融术后复发率就上升7.2%。另外，与正常直径相比，左房中度扩张(LAD: 40 ～ 50 mm)和重度扩张(LAD > 50 mm)的房颤患者术后复发率分别增加1.30和2.14倍[16]。D′Ascenzo等[17]进行了一项大样本的研究，包含4 357例阵发性房颤和1 777例持续性房颤患者，发现LAD > 50 mm是消融术后房颤复发的一个强有力的预测因子。Tzou等[18]、Montserrat等[19]和 Lo等[20]的研究均有类似发现，LAD越大，术后房颤复发率可能越高。

另外，考虑到左房大小与体形存在明显关系，有研究在测得LAD后除以体表面积得到左房直径指数(left atrial diameter index,LADI)。Shin等[21]选取消融术前左房前后径(胸骨旁长轴观)、左房上下径(心尖四腔观)，计算得到LADI，发现消融术后房颤复发组和未复发组左房前后LADI、上下LADI都具有统计学差异[(25.9 ± 4.4 )mm/m2vs ( 22.5 ± 2.9 ) mm/m2、 ( 34.0 ± 5.2 )mm/m2vs ( 29.3 ± 3.3 ) mm/m2,P均= 0.01]。

可见，LAD是房颤复发理想的预测因子。而LADI进一步减弱了不同体形对LAD基础值的影响，其预测效益可能更高。

2.2左房容积(left atrial volume ,LAV) 由于左房形状不规则，单个切面上的直径不能充分反映整个心房重构的程度。LAV预测消融术后房颤复发的效益可能优于LAD。另外，超声检查中心尖四腔观能完全暴露整个左房，此切面评价LAV优于胸骨旁两腔观[22]。Montserrat等[19]对154例房颤病人的研究中，发现LAV > 82.35 ml是首次消融术后房颤复发的预测因子(特异性 96% )。以研究对象中位数年龄(54岁)分组，年龄≤54岁的房颤未复发组和复发组间LAV具有统计学差异[(50.7 ± 12.9 ) ml vs ( 67.7 ±24.1 ) ml，P=0.04]，而年龄>54岁两组间LAV无显著差异[(52.0 ± 6.2 ) ml vs ( 54.2 ± 17.4 ) ml，P=0.82]，说明复发组与未复发组间的LAV在年轻患者中差异更明显。

与LAD相同，LAV也与体形相关。有研究在测得LAV后除以体表面积得到左房容积指数(left atrial volume index ,LAVI)。Shin等[21]发现术前LAVI > 34 ml/m2是消融术后房颤复发的预测因子(敏感性70% ，特异性91%)。Kohari等[22]认为LAVI > 26 ml/m2是房颤复发的预测因子。den Uijl等[23]发现消融术后房颤复发组的LAVI明显大于未复发组[ ( 46.06 ± 16.9 ) ml/m2vs ( 40.26 ± 14.1 ) ml/m2，P=0.016]。

2.3结构性预测因子的研究存在分歧 最近有几项研究认为，导管消融术后房颤复发组与未复发组的LAD或LAV无差异[24-26]。多种原因可能引起这种分歧。上述Montserrat等[19]对房颤复发组与未复发组术前LAV的研究中，不同年龄分层两组间的LAV差异性不同，表明研究对象的年龄异质性可能会对研究结果产生影响。此外，上述研究房颤类型、消融术式和随访时间均存在差异，都可能影响预测效益。同时，超声在检测结构性预测因子时误差较大：左房不规则的形状使LAD评价左房大小存在缺陷；拖带效应(即周围组织牵拉)和角度偏差降低了检测指标的可靠性[27]。即便如此，也不能完全否定结构性预测因子对消融术后房颤复发的预测效益。

3 功能性预测因子引起广泛的关注

与房颤相关的心脏结构改变是一个历时较长的过程[3, 28]。山羊的动物模型中，在心房结构性重构能被检测之前，房颤的性质早已稳定[3]。因此，用左房结构来预测房颤复发就显得相对滞后，对房颤复发的二级预防意义不大。而心房超微结构的改变相对较早发生，这种改变由心肌细胞能量的产生和利用出现缺陷引起，包括心肌细胞内糖原累积、收缩结构消失和线粒体外形变异[29]。在阵发性房颤患者的早期病程中，左房的结构性重构还未能被监测到，功能性重构的预测因子此时就体现出了优越性[30]。而且，在组织多普勒成像基础上发展的新技术如应变率成像、二维斑点追踪成像、实时三维超声心动图等在评价左房功能时能有效减少检测过程中的误差[31-33]。因此，左房的功能性重构与房颤复发的关系引起广泛关注。

3.1左心耳血流速度(left atrial appendage flow velocity ,LAAV) LAAV可作为左房储存器功能和收缩功能的评估指标[34]。心房纤维化时，左心耳通过其自身的伸展性来调节左房压力-容量关系，以增强血流动力学功能[35]。Gerede等[14]在51例阵发性房颤患者消融术后1年的随访中发现，房颤复发组的LAAV小于未复发组[(25.00 ± 9.16 )cm/s vs ( 56.00 ± 26.72 ) cm/s,P< 0.000 ]，LAAV ≤ 30 cm/s是消融术后房颤复发的预测因子(敏感性85%，特异性95%)。其他的研究还报道了LAAV > 28 cm/s(敏感性62%，特异性69%)[36]，> 30 cm/s (敏感性77.8%，特异性72.8%)[37],> 31 cm/s(敏感性约40%，特异性约80%)[38],> 40 cm/s(敏感性56%，特异性80%)[39]是消融成功的独立性预测因子，但后两项研究的结果的敏感性相对较低。

3.2左房和左室血流速度 多普勒超声测得的心腔中血流速度，如E、e′、A等(E：舒张早期最大峰值流速，e′：舒张早期跨二尖瓣环流速，A：舒张晚期最大峰值流速)，可以反应左房和左室中的压力梯度[40]。左房、左室血流速度的下降提示左室舒张功能障碍，左室顺应性降低，使左房长时间处于压力过载的情况下，促进房颤的发生和维持[41]。Chung等[42]对66例房颤消融术后患者随访中，发现E/e′值> 9.15是消融术后房颤复发的预测因子(敏感性75%，特异性73.1%)。

另外，有最新的研究引入Sa(收缩期跨二尖瓣环流速)、Aa(舒张晚期跨二尖瓣环流速)，Sa与左心室收缩功能有关[43]，所以 E/( e′*Sa)和Ea/(Aa*Sa)的值就能同时反应左心室的收缩和舒张功能。在对73例消融术后房颤患者的随访中发现，E/( e′×Sa)和Ea/(Aa×Sa)比E/e′值预测消融术后房颤复发更敏感[44]。

3.3左房射血分数(left atrial emptying fraction ,LAEF) LAEF=(左房最大容积-左房最小容积) / 左房最大容积×100%。LAEF是公认的左房储存功能和管道功能的代表因子，检测方法相对简单可行[45]。Kim等[45]在130例房颤消融术后患者2年的随访中发现，房颤复发组的LAEF低于未复发组[ (28.1 ± 7.7 ) % vs ( 31.4 ± 9.4 ) %,P=0.034]，LAEF < 20%是消融术后房颤复发的预测因子(敏感性69%，特异性84%)。在Lim等[46]的研究中，定义LAEFactive = 100 ×(心电图上p波出现时的左房容积-左房最小容积)/ 心电图p波出现时的左房容积，发现LAEFactive < 23.5% 是消融术后房颤复发的预测因子(敏感性66.7%，特异性63.6%)。

3.4左房应变(left atrial strain ,LAS) LAS(左房内径的变化值占原内径的百分比)是基于左房形变的功能参数，反应了心肌的生理力学特性[47-48]，其结果不受心脏整体运动和拖带效应的影响，测值相对准确而客观[31]。Hong等[49]发现LAS降低是消融术后3个月房颤复发的唯一预测因子。另外，LAS在区分孤立性房颤患者和健康人的效能优于LAV，因此LAS比LAV更有效地反应左房重构[49]。其他类似的研究在消融术后的随访中发现术前LAS > 20%(敏感性86%，特异性70%)[26]、LAS > 23.2%(敏感性76%，特异性66%)[50]是房颤患者保持窦性心律的预测因子。Ma等[51]汇总了8项关于LAS与消融术后房颤复发关系的研究，总样本量高达686例，发现消融术后房颤复发组的LAS小于未复发组，LAS≤22.8%为消融术后房颤复发的预测因子(敏感性78%，特异性75%)。

左房侧壁不受右房和肺静脉影响，左房侧壁的应变能最真实地反应左房肌肉的收缩能力和左房的功能[30]。Yasuda等[30]对100名房颤患者1年的随访中，发现以左房侧壁的应变(left atrial lateral strain ,LA-LS=心室收缩时左房侧壁的应变—心房收缩时左房侧壁的应变)<25.27%作为消融术后房颤复发的预测因子(敏感性81%，特异性82%)，其预测效益优于LAS。

3.5估计肺动脉楔压(estimated pulmonary capillary wedge Pressure , ePCWP) ePCWP[10.8-12.4×log10(AEFactive / LAVImin)]是采用斑点追踪超声监测动力学追踪指数来估算的指标，它结合了房颤复发的功能性预测因子(LAEF)和结构性预测因子(LAVI)，比单独使用左房功能或结构因子来评估消融预后效益高。Kawasaki等[52]发现ePCWP< 13 mmHg是消融术后房颤复发的预测因子(敏感性73%，特异性77%)。

消融术后房颤复发的功能性预测因子种类较多、各有特点，综合分析其敏感性和特异性大多具有较准确的预测价值。并且其在预测效益上较结构性预测因子具有优越性，临床上可以参考这些超声参数筛选适合消融手术的房颤患者。

4 结论

超声监测的结构性预测因子虽然得到广泛认可，但受多种因素影响、检测误差大、缺乏统一的标准等限制，不应该作为预测消融结果的唯一因素。随着新型超声设备的使用，功能性参数能为左房状态提供额外的信息，并且都被证明是消融术后房颤复发的独立预测因子。这些检测在临床上方便可行，检测结果可信度高，可被广泛运用以指导临床治疗策略，使房颤患者获益。

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