2016 ESC/EACTS 心房颤动管理指南

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ESC GUIDELINES 无锡明慈心血管病医院孙凌翻译, 柳州市人民医院心内科胡世红审核, 编辑:屈胜胜,医脉通核发, 加入我们:http://dy.medlive.cn/view.php?id=395034 2016 ESC/EACTS 心房颤动管理指南 欧洲心脏病学会(ESC)心房颤动管理工作组 ESC 欧洲心律协会(EHRA)为此做出特别贡献 欧洲卒中组织(ESO)认可 作者/工作组成员:Paulus Kirchhof* (主席) (英国/德国) Stefano Benussi* 1 (共同主席) (瑞士), Dipak Kotecha (英国), Anders Ahlsson 1 (瑞典), Dan Atar (挪威), Barbara Casadei (英国), Manuel Castella 1 (西班 ), Hans-Christoph Diener 2 (德国), Hein Heidbuchel (比利时), Jeroen Hendriks (荷兰), Gerhard Hindricks (德国),Antonis S. Manolis (希腊), Jonas Oldgren (瑞典), Bogdan Alexandru Popescu (罗马尼亚), Ulrich Schotten (荷兰), Bart Van Putte1 (荷兰),and Panagiotis Vardas (希腊) 文献审阅成员:Stefan Agewall (临床实践指南审查协调员) (挪威), John Camm (临床实践指南审查协调员) (英国), Gonzalo Baron Esquivias (西班牙), Werner Budts (比利时), Scipione Carerj (意大利), Filip Casselman (比利时), Antonio Coca (西班牙), Raffaele De Caterina (意大利), Spiridon Deftereos (希腊), Dobromir Dobrev (德国), Jose M. Ferro (葡萄牙), Gerasimos Filippatos (希腊), Donna Fitzsimons (英国), Bulent Gorenek (土耳其), Maxine Guenoun (法国), Stefan H. Hohnloser (德国), Philippe Kolh (利时), Gregory Y. H. Lip (英国), Athanasios Manolis (希腊), John McMurray (英国), Piotr Ponikowski (波兰), Raphael Rosenhek (地利), Frank Ruschitzka (瑞士), Irina Savelieva (英国), Sanjay Sharma (英国), Piotr Suwalski (波兰), Juan Luis Tamargo (西班牙), Clare J. Taylor (英国), Isabelle C. Van Gelder (荷兰), Adriaan A. Voors (荷兰), Stephan Windecker (瑞士), Jose Luis Zamorano (西班 ), and Katja Zeppenfeld (荷兰) 参与这一指南的所有专家的公开信息可在 ESC 网页查阅 http://www.escardio.org/guidelines. 关键词: 指南;心房颤动;抗凝治疗;维生素 K 拮抗剂;非维生素 K 拮抗剂类口服抗凝剂; 左心耳封堵;心率控制;复律;节律控制;抗心律失常药物;上游治疗;导管消 融;AF 外科手术;瓣膜修复;肺静脉隔离;左心房消融 目录 1.序言.......................................................................................... 6 2.前言.......................................................................................... 7 3.流行病学和对患者的影响...................................................... 7 3.1 心房颤动的发病率和患病率............................................ 7 3.2 心房颤动的致残致残率、死亡率和卫生保健负担 ........ 8 3.3 循证管理对心房颤动患者结局转归的影响.................... 8 3.4 性别 ................................................................................... 9 4.指导管理的病理生理学和遗传因素 .................................... 10 4.1 遗传倾向 ......................................................................... 10 4.2 导致心房颤动的机制 ..................................................... 10 4.2.1 心房结构重构和离子通道功能.............................. 10 4.2.2 心房颤动的电生理机制 ......................................... 10 4.2.2.1 心房颤动的局灶启动和维持.................. 11 4.2.2.2 多子波假说和心房颤动的转子起源 ..... 11 5.心房颤动的诊断和及时检出 ................................................ 12 5.1 显性和隐匿性心房颤动 ................................................. 12 5.2 隐匿性心房颤动的筛查 ................................................. 12 5.2.1 在社区通过心电图筛查心房颤动......................... 12 5.2.2 阵发性心房颤动的延长监测 ................................ 14 5.2.3 带有起搏器和植入性器械的患者 .......................... 14 5.2.4 卒中幸存者中心房颤动的检出 .............................. 15 5.3 心房扑动的心电图检测 .................................................. 15 6.心房颤动的分类 .................................................................... 16 6.1 心房颤动类型.................................................................. 16 6.2 反映不同的心律失常病因的心房颤动类型 .................. 17 6.3 心房颤动的症状负荷...................................................... 18 7.危险因素和伴随的心血管疾病的检出和管理..................... 19 7.1 心力衰竭......................................................................... 19 7.1.1 伴有射血分数降低的心力衰竭的心房颤动患者 .. 21 7.1.2 伴有射血分数保留的心力衰竭的心房颤动患者 .. 21 7.1.3 伴有射血分数中间值的心力衰竭的心房颤动患者 22 7.1.4 心力衰竭患者中心房颤动的预防 ......................... 22 7.2 高血压.............................................................................. 22 7.3 瓣膜性心脏病.................................................................. 23 7.4 糖尿病.............................................................................. 23 7.5 肥胖和减肥...................................................................... 23 7.5.1 肥胖是一种危险因素............................................. 23

Transcript of 2016 ESC/EACTS 心房颤动管理指南

Page 1: 2016 ESC/EACTS 心房颤动管理指南

ESC GUIDELINES

无锡明慈心血管病医院孙凌翻译,

柳州市人民医院心内科胡世红审核,

编辑:屈胜胜,医脉通核发,

加入我们:http://dy.medlive.cn/view.php?id=395034

2016 ESC/EACTS 心房颤动管理指南

欧洲心脏病学会(ESC)心房颤动管理工作组

ESC 欧洲心律协会(EHRA)为此做出特别贡献

欧洲卒中组织(ESO)认可

作者/工作组成员:Paulus Kirchhof* (主席) (英国/德国) Stefano Benussi*1 (共同主席) (瑞士), Dipak

Kotecha (英国), Anders Ahlsson1 (瑞典), Dan Atar (挪威), Barbara Casadei (英国), Manuel Castella1 (西班

牙), Hans-Christoph Diener2 (德国), Hein Heidbuchel (比利时), Jeroen Hendriks (荷兰), Gerhard Hindricks

(德国),Antonis S. Manolis (希腊), Jonas Oldgren (瑞典), Bogdan Alexandru Popescu (罗马尼亚), Ulrich

Schotten (荷兰), Bart Van Putte1 (荷兰),and Panagiotis Vardas (希腊)

文献审阅成员:Stefan Agewall (临床实践指南审查协调员) (挪威), John Camm (临床实践指南审查协调员) (英国), Gonzalo

Baron Esquivias (西班牙), Werner Budts (比利时), Scipione Carerj (意大利), Filip Casselman (比利时), Antonio Coca (西班牙),

Raffaele De Caterina (意大利), Spiridon Deftereos (希腊), Dobromir Dobrev (德国), Jose M. Ferro (葡萄牙), Gerasimos Filippatos

(希腊), Donna Fitzsimons (英国), Bulent Gorenek (土耳其), Maxine Guenoun (法国), Stefan H. Hohnloser (德国), Philippe Kolh (比

利时), Gregory Y. H. Lip (英国), Athanasios Manolis (希腊), John McMurray (英国), Piotr Ponikowski (波兰), Raphael Rosenhek (奥

地利), Frank Ruschitzka (瑞士), Irina Savelieva (英国), Sanjay Sharma (英国), Piotr Suwalski (波兰), Juan Luis Tamargo (西班牙),

Clare J. Taylor (英国), Isabelle C. Van Gelder (荷兰), Adriaan A. Voors (荷兰), Stephan Windecker (瑞士), Jose Luis Zamorano (西班

牙), and Katja Zeppenfeld (荷兰)

参与这一指南的所有专家的公开信息可在 ESC 网页查阅 http://www.escardio.org/guidelines.

关键词: 指南;心房颤动;抗凝治疗;维生素 K 拮抗剂;非维生素 K 拮抗剂类口服抗凝剂;

左心耳封堵;心率控制;复律;节律控制;抗心律失常药物;上游治疗;导管消

融;AF 外科手术;瓣膜修复;肺静脉隔离;左心房消融

目录

1.序言 .......................................................................................... 6

2.前言 .......................................................................................... 7

3.流行病学和对患者的影响 ...................................................... 7

3.1 心房颤动的发病率和患病率 ............................................ 7

3.2 心房颤动的致残致残率、死亡率和卫生保健负担 ........ 8

3.3 循证管理对心房颤动患者结局转归的影响 .................... 8

3.4 性别 ................................................................................... 9

4.指导管理的病理生理学和遗传因素 .................................... 10

4.1 遗传倾向 ......................................................................... 10

4.2 导致心房颤动的机制 ..................................................... 10

4.2.1 心房结构重构和离子通道功能.............................. 10

4.2.2 心房颤动的电生理机制 ......................................... 10

4.2.2.1 心房颤动的局灶启动和维持 .................. 11

4.2.2.2 多子波假说和心房颤动的转子起源 ..... 11

5.心房颤动的诊断和及时检出 ................................................ 12

5.1 显性和隐匿性心房颤动 ................................................. 12

5.2 隐匿性心房颤动的筛查 ................................................. 12

5.2.1 在社区通过心电图筛查心房颤动 ......................... 12

5.2.2 阵发性心房颤动的延长监测 ................................ 14

5.2.3 带有起搏器和植入性器械的患者 .......................... 14

5.2.4 卒中幸存者中心房颤动的检出 .............................. 15

5.3 心房扑动的心电图检测 .................................................. 15

6.心房颤动的分类 .................................................................... 16

6.1 心房颤动类型 .................................................................. 16

6.2 反映不同的心律失常病因的心房颤动类型 .................. 17

6.3 心房颤动的症状负荷 ...................................................... 18

7.危险因素和伴随的心血管疾病的检出和管理 ..................... 19

7.1 心力衰竭 ......................................................................... 19

7.1.1 伴有射血分数降低的心力衰竭的心房颤动患者 .. 21

7.1.2 伴有射血分数保留的心力衰竭的心房颤动患者 .. 21

7.1.3 伴有射血分数中间值的心力衰竭的心房颤动患者

22

7.1.4 心力衰竭患者中心房颤动的预防 ......................... 22

7.2 高血压 .............................................................................. 22

7.3 瓣膜性心脏病 .................................................................. 23

7.4 糖尿病 .............................................................................. 23

7.5 肥胖和减肥 ...................................................................... 23

7.5.1 肥胖是一种危险因素 ............................................. 23

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7.5.2 肥胖心房颤动患者的减肥 ..................................... 24

7.5.3 肥胖患者的导管消融 ............................................ 24

7.6 慢性阻塞性肺疾病,睡眠呼吸暂停和其他呼吸道疾病

................................................................................................... 24

7.7 慢性肾脏病 ..................................................................... 25

8.心房颤动患者的整体管理 .................................................... 25

8.1 支持心房颤动整体照护的证据 ...................................... 28

8.2 心房颤动整体照护的组成部分 ...................................... 28

8.2.1 患者参与 ................................................................ 28

8.2.2 多学科心房颤动团队 ............................................ 28

8.2.3 非专业人员的作用 ................................................ 28

8.2.4 用于支持心房颤动照护的技术............................. 28

8.3 心房颤动患者的诊断性检查 .......................................... 29

8.3.1 对所有心房颤动患者推荐的评估措施 ................. 29

8.3.2 在特定心房颤动患者中的额外检查 ...................... 29

8.4 结构化的随访 ................................................................. 29

8.5 心房颤动管理目标的确定 ............................................. 29

9.心房颤动患者中的卒中预防治疗 ........................................ 30

9.1 卒中和出血风险的预测 ................................................. 30

9.1.1 卒中和系统性栓塞的临床风险评分 ..................... 30

9.1.2 在 CHA2DS2-VASc 评分 1 分的男性和 2 分的女性

患者中的抗凝治疗 ................................................................... 30

9.1.3 出血的临床风险评分 ............................................ 31

9.2 卒中预防 ........................................................................ 33

9.2.1 维生素 K 拮抗剂 ................................................... 33

9.2.2 非维生素 K 拮抗剂类口服抗凝剂 ........................ 33

9.2.2.1 阿哌沙班 ................................................. 33

9.2.2.2 达比加群 ................................................. 34

9.2.2.3 依度沙班 ................................................. 34

9.2.2.4 利伐沙班 ................................................. 34

9.2.3 非维生素 K 拮抗剂类口服抗凝剂还是维生素 K 拮

抗剂 34

9.2.4 合并慢性肾病的心房颤动患者中的口服抗凝治疗

37

9.2.5 透析的心房颤动患者的口服抗凝治疗 ................. 37

9.2.6 需要进行肾脏移植的心房颤动患者 ..................... 38

9.2.7 抗血小板治疗能否作为口服抗凝剂的替代 ......... 38

9.3 左心耳封堵和切除 ........................................................ 38

9.3.1 左心耳封堵器械 .................................................... 38

9.3.2 外科左心耳封堵或切除 ........................................ 38

9.4 卒中的二级预防 ............................................................ 40

9.4.1 急性缺血性卒中的治疗 ........................................ 40

9.4.2 短暂性脑缺血发作或缺血性卒中后启动抗凝治疗

40

9.4.3 颅内出血后启动抗凝治疗 .................................... 41

9.5 减少抗凝治疗出血的策略.............................................. 42

9.5.1 未控制的高血压 .................................................... 42

9.5.2 既往出血事件 ........................................................ 42

9.5.3 波动的国际标准化比值和适当的非维生素 K 拮抗

剂类口服抗凝剂剂量 ............................................................... 42

9.5.4 酗酒 ........................................................................ 43

9.5.5 跌倒和痴呆 ............................................................ 43

9.5.6 基因检测 ................................................................ 43

9.5.7 口服抗凝剂的桥接 ................................................ 43

9.6 抗凝治疗的心房颤动患者出血事件的管理 ................. 43

9.6.1 轻度、中等和严重出血的管理............................. 43

9.6.2 存在出血风险或出血事件的心房颤动患者的口服

抗凝治疗 ................................................................................... 45

9.7 口服抗凝剂和抗血小板药物的联合治疗 ..................... 46

9.7.1 需要口服抗凝剂治疗的患者在急性冠脉综合征和

经皮冠状动脉介入后的抗栓治疗 ............................................ 46

10. 心房颤动的心室率控制治疗 ............................................. 49

10.1 急诊心室率控制 ........................................................... 49

10.2 长期药物控制心室率 ................................................... 49

10.2.1 β阻滞剂 ............................................................... 49

10.2.2 非二氢吡啶类钙拮抗剂 ....................................... 51

10.2.3 洋地黄 ................................................................... 51

10.2.4 胺碘酮 ................................................................... 52

10.3 心房颤动患者的心率控制目标 ................................... 52

10.4 房室结消融和起搏 ....................................................... 52

11. 心房颤动节律控制治疗 ..................................................... 53

11.1 急诊转复为窦性心律 ................................................... 53

11.1.1 抗心律失常药物急诊转复窦性心律(药物复律)

54

11.1.2 患者自行用“口袋中的药片”复律 ................... 54

11.1.3 电复律 ................................................................... 54

11.1.4 复律患者的抗凝治疗 ........................................... 55

11.2 长期抗心律失常药物治疗 ........................................... 55

11.2.1 长期抗心律失常药物治疗的选择:安全第一! 56

11.2.1.1 胺碘酮 ................................................... 56

11.2.1.2 决奈达隆 ............................................... 57

11.2.1.3 氟卡尼和普罗帕酮 ............................... 57

11.2.1.4 奎尼丁和丙吡胺 ................................... 57

11.2.1.5 索他洛尔 ............................................... 58

11.2.1.6 多非利特 ............................................... 58

11.2.2 十二导联心电图作为识别存在促心律失常风险患

者的工具 ................................................................................... 58

11.2.3 新型抗心律失常药物 ........................................... 58

11.2.4 非抗心律失常药物的抗心律失常作用 ............... 60

11.3 导管消融 ....................................................................... 64

11.3.1 适应证 ................................................................... 64

11.3.2 技巧和技术 ........................................................... 64

11.3.3 转归和并发症 ....................................................... 64

11.3.3.1 心房颤动导管消融的转归.................... 64

11.3.3.2 心房颤动导管消融的并发症 ................ 65

11.3.4 抗凝治疗:消融前、消融中和消融后 ............... 65

11.3.5 心力衰竭患者中的心房颤动消融 ....................... 66

11.3.6 导管消融后的随访 ............................................... 66

11.4 心房颤动外科治疗 ....................................................... 66

11.4.1 伴随进行的心房颤动外科手术 ........................... 66

11.4.2 单独进行的节律控制外科手术 ........................... 68

11.5 治疗失败后的节律控制选择 ....................................... 69

11.6 心房颤动的心脏团队 ................................................... 69

12 杂交节律控制治疗 ............................................................. 71

12.1 抗心律失常药物和导管消融联合治疗 ....................... 71

12.2 抗心律失常药物和起搏器联合治疗 ........................... 71

13. 特殊情况 ............................................................................ 71

13.1 虚弱和“高龄”患者 ................................................... 71

13.2 遗传性心肌病、离子通道病和旁路 ........................... 71

13.2.1 WPW 综合征 ......................................................... 71

13.2.2 肥厚型心肌病 ....................................................... 72

13.2.3 离子通道病和致心律失常性右室心肌病 ........... 73

13.3 运动和心房颤动 ........................................................... 74

13.4 妊娠 ............................................................................... 74

13.4.1 室率控制 ............................................................... 74

13.4.2 节律控制 ............................................................... 75

13.4.3 抗凝治疗 ............................................................... 75

13.5 术后心房颤动 ............................................................... 75

13.5.1 术后心房颤动的预防 ........................................... 75

13.5.2 抗凝治疗 ............................................................... 76

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13.5.3 术后心房颤动的节律控制治疗 ........................... 76

13.6 成人先天性心脏病患者的房性心律失常 ................... 76

13.6.1 成人先天性心脏病患者房性心律失常的一般治疗

76

13.6.2 房性心律失常和房间隔缺损................................ 77

13.6.3 Fontan 术后的快速性房性心律失常 .................... 77

13.6.4 法洛氏四联征矫治术后的快速性房性心律失常 77

13.7 心房扑动的管理 .......................................................... 77

14.患者参与,教育和自我管理 .............................................. 78

14.1 以患者为中心的照护 .................................................. 78

14.2 一体化患者教育 .......................................................... 79

14.3 自我管理和共同决策 .................................................. 79

15 证据缺口 ............................................................................. 79

15.1 引起心房颤动的主要健康因素 ................................... 79

15.2 有多少心房颤动需要治疗? ..................................... 79

15.3 心房高频事件和抗凝需求 ........................................... 80

15.4 特殊人群中的卒中风险................................................ 80

15.5 严重慢性肾病患者中的抗凝治疗 ............................... 80

15.6 左心耳封堵预防卒中 .................................................. 80

15.7 心房颤动患者出血或卒中事件后的抗凝治疗 ........... 80

15.8 非急诊复律的抗凝治疗和最佳时间 ........................... 80

15.9 心房颤动患者中卒中或短暂性脑缺血发作的竞争性病

因 ............................................................................................... 80

15.10 生物瓣膜(包括经导管主动脉瓣植入)和非风湿性瓣

膜病瓣膜病患者的抗凝 ............................................................ 81

15.11 “成功”导管消融后的抗凝治疗 ............................. 81

15.12 室率控制药物的比较 ................................................. 81

15.13 持续性和长程持续性 AF 的导管消融 ....................... 81

15.14 重复导管消融的最佳技术 ......................................... 81

15.15 维持窦性心律的联合治疗 ......................................... 81

15.16 心房颤动患者中节律控制治疗能够带来预后获益吗?

................................................................................................... 81

15.17 经胸腔镜“单独”心房颤动外科治疗 ..................... 81

15.18 外科切除左心耳 ......................................................... 82

15.19 伴随进行心房颤动外科手术 ..................................... 82

16. 指南中做和不做的信息 ..................................................... 83

17. 心房颤动患者管理的简短总结 ......................................... 86

17. 心房颤动患者管理的简短总结 ......................................... 86

18. 网页附录 ............................................................................ 86

19. 附录 .................................................................................... 87

20. 参考文献 ............................................................................ 87

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缩略语

ABC 年龄,生物标记物,临床病史

ACE 血管紧张素转换酶

ACS 急性冠脉综合征

AF 心房颤动

AFFIRM 心房颤动节律管理的随访研究

AFNET 德国能力网络对心房颤动的研

AngⅡ 血管紧张素Ⅱ

AHER 心房高频事件

APACHE-AF 心房颤动患者在抗凝相关颅内

出血后应用阿哌沙班、抗血小

板药物或不使用抗栓药物的比

ARB 血管紧张素受体拮抗剂

ARISTOTLE 阿哌沙班降低心房颤动卒中和

其他血栓栓塞事件的研究

ARNI 血管紧张素受体脑啡肽酶抑制

ARTESiA 阿哌沙班降低器械检出亚临床

心房颤动患者的血栓栓塞风险

AV 房室的

AXAFA 在心房颤动导管消融时使用直

接 Xa 因子抑制剂阿哌沙班抗

凝:与维生素 K 拮抗剂的比较

BAFTA 伯明翰老年患者心房颤动治疗

研究

BMI 体质指数

b.p.m 次/分

CABANA 导管消融与抗心律失常药物治

疗房颤的试验

CABG 冠状动脉旁路移植术

CAD 冠状动脉性心脏病

CHA2DS2-

VASc

充血性心力衰竭,高血压,年

龄≥75(2 分),糖尿病,卒中

(2 分),血管疾病,年龄 65-

74 岁,性别(女性)

CHADS2 心力衰竭,高血压,年龄,糖

尿病,卒中(2 分)

CI 可信区间

CKD 慢性肾脏疾病

CPG 实践指南委员会

CrCl 肌酐清除率

CT 计算机体层成像

CV 心血管

CYP2D6 细胞色素 P450 2D6

CYP3A4 细胞色素 P450 3A4

DIG 洋地黄研究组

EACTS 欧洲心胸外科学会

EAST 早期治疗心房颤动预防卒中试

ECG 心电图

EHRA 欧洲心律协会

ENGAGE AF-

TIMI 48

使用新一代 Xa 有效抗凝治疗心

房颤动——心肌梗死溶栓治疗

48

EORP 欧洲观察性研究项目

ESC 欧洲心脏病学会

ESO 欧洲卒中组织

FAST 心房颤动导管消融与外科消融

治疗的比较

FEV1 1 秒用力呼气量

FFP Ⅳ因子凝血酶原复合物浓缩剂

FⅫ Ⅻ因子

GDF-15 生长分化因子 15

GFR 肾小球滤过率

GUCH 成人先天性心脏病

HARMONY 评估单独或联合应用雷诺嗪和

决奈达隆治疗阵发性心房颤动

患者效果的研究

HAS-BLED 高血压,肾功能/肝功能异常

(每项 1 分),卒中,出血病

史或出血倾向,INR 不稳定,

老年(>65 岁),合并使用药

物/酒精(每项 1 分)

HEMORR2-

HAGES

肝病或肾病,酒精滥用,恶性

肿瘤病史,老年(>75 岁),

血小板数量/功能下降/抗血小板

药物,再出血风险(2 分),高

血压(未控制),贫血,遗传

因素,额外的跌倒风险,卒中

病史

HF 心力衰竭

HFmrEF 射血分数中间值的心力衰竭

HFpEF 射血分数保留的心力衰竭

HFrEF 射血分数降低的心力衰竭

HR 风险比

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ICD 植入式心律转复除颤器

IHD 缺血性心脏病

IL-6 白介素 6

INR 国际标准化比值

i.v. 静脉注射

LA 左心房/左心房的

LAA 左心耳

LAAOS 左心耳封堵研究

LV 左心室的

LVEF 左心室射血分数

LVH 左心室肥厚

MANTRA-

PAF

阵发性心房颤动抗心律失常药

物或射频消融治疗

MERLIN 雷诺嗪治疗非 ST 段抬高性急性

冠脉综合征降低心肌缺血的代

谢效率

MRA 盐皮质激素(醛固酮)受体拮

抗剂

MRI 磁共振成像

NIHSS 美国国立卫生研究院卒中严重

程度量表

NOAC 非维生素 K 拮抗剂类口服抗凝

NOAH 非维生素 K 拮抗剂类口服抗凝

剂治疗心房高频事件患者

NYHA 纽约心脏协会

OAC 口服抗凝/口服抗凝剂

OR 比数比

ORBIT 更好治疗心房颤动的结局注册

研究

PAFAC 复律后预防心房颤动试验

PAI-1 纤溶酶原激活物抑制剂 1

PCI 经皮冠状动脉介入治疗

PCC 凝血酶原复合体浓缩物

PICOT 人群、干预、比较、结局、时

PREVAIL 心房颤动患者中 Watchman 左

心耳封堵器与长期华法林治疗

的前瞻性随机化评估试验

PROTECT AF 在心房颤动患者中 Watchman

左心耳封堵系统预防血栓的试

PUFA 多不饱和脂肪酸

PVI 肺静脉隔离

QoL 生活质量

RACE 永久性心房颤动中室率控制的

效果

RATE-AF 永久性心房颤动中室率控制治

疗评估

RCT 随机化对照试验

RE-CIRCUIT 在肺静脉消融时随机化评估达

比加群酯与华法林:不间断的

围手术期抗凝策略

RE-LY 长期抗凝治疗的随机化评估

RF 射频消融

ROCKET-AF 心房颤动中比较每日一次口服

直接 Xa 因子抑制剂利伐沙班与

维生素 K 拮抗剂预防卒中和栓

塞的试验

RR 危险比

rtPA 重组组织型纤溶酶原激活剂

SAMe-TT2R2 性别(女性),年龄(<60

岁),病史(以下两项或以

上:高血压、糖尿病、心肌梗

死、外周血管疾病、充血性心

力衰竭、卒中史、肺部疾病,

肝病或肾病),治疗(药物相

互作用,如胺碘酮),吸烟(2

年内,2 分),种族(非高加索

人,2 分)

SD 标准差

SPAF 心房颤动患者的卒中预防

SR 窦性心律

TF 组织因子

TIA 短暂性脑缺血发作

TIMI 心肌梗死溶栓治疗

TOE 经食道超声心动图

TTR 治疗范围内时间百分比

UFH 普通肝素

VKA 维生素 K 拮抗剂

VT 室性心动过速

VVI 心室起搏、心室感知、感知后

抑制起搏器

WOEST 植入了冠状动脉支架的口服抗

凝患者,最优化的抗血小板和

抗凝治疗是什么?

WPW WPW 综合征

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1.序言

在写作过程中,指南总结和评估了针对一个特定问题的所有可用证据,以帮助医护人员在既定的情况

下,考虑对转归的影响以及特定的诊断或治疗方法的风险效益比,旨在帮助健康专业人员为每一位患者选

择最佳的管理策略。指南和推荐应当帮助健康专业人员在其日常实践中作决定。然而,关于一位患者的最

终决定必须由负责任的健康专业人员在与患者和照顾者适当协商后作出。

近年来,欧洲心脏病学会(ESC)、欧洲心胸外科协会(EACTS)以及其他协会与组织已出版了大量

指南。由于对临床实践的影响,已制定了写作指南的质量标准,以使所有的决定对用户透明。ESC 指南推

荐的形成和出版均可在 ESC 网页上查阅(http://www.escardio.org/Guidelines-&-Education/Clinical-Practice-

Guidelines/Guidelines-development/Writing-ESC-Guidelines)。ESC 指南代表针对某一主题的官方立场并定

期更新。

工作组成员由 ESC 选择,包括来自于欧洲心律协会(EHRA)、EACTS 以及欧洲卒中组织(ESO)的

成员,以代表参与此类疾病医疗护理的医学专业人士。经选择的该领域的专家根据 ESC 实践指南委员会

(CPG)的政策,对特定疾病的管理(包括诊断、治疗、预防和康复)已发表的证据进行了全面的审查,

并得到了 EACTS 和 ESO 的认可。对诊断和治疗程序进行了关键评估,包括对风险-效益比的评估。只要有

相关数据,对更大人群的预期健康结局也进行了评估。根据预先定义的标准对证据水平和推荐强度进行权

重和分级,如表 1 和表 2 所述。

表 1 推荐类别

推荐

类别

定义 推荐所

用措词

Ⅰ类 特定治疗或操作的证据和/或一般意见是有益、有用、有效的。 给予推荐 /是适

应证

Ⅱ类 特定治疗或操作的有用/有效,其证据存在矛盾和/或意见不一

致。

Ⅱa 类 证据/意见的权衡支持有用/有效。 应当考虑

Ⅱb 类 有用/有效未经证据/意见充分明确。 可以考虑

Ⅲ类 特定治疗或操作的证据或一般意见是无用/无效的,在某些情况

下可能是有害的

不推荐

表 2 证据水平

证据水平 A 数据来源于多个随机临床试验或汇总分析

证据水平 B 数据来源于单个随机临床试验或大型非随机研究

证据水平 C 专家意见共识和/或小型研究、回顾性和注册研究

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写作和审阅小组的专家为所有可能被视为存在现实或潜在利益冲突来源的关系提供了利益声明表单。

这些表单汇编为文件,可在 ESC 网页上查阅(http://www.escardio.org/guidelines)。在写作期间利益声明的

任何变化都会告知 ESC 和 EACTS,并进行更新。工作组的所有财政支持来自于 ESC 和 EACTS,与医疗

保健企业没有任何牵连。

ESC CPG 监督并协调工作组、专家组或共识小组制定新指南。委员会还负责保证这些指南的进程。

ESC 指南广泛接受 CPG 专家和外部专家的审阅,而本指南还接受了由 EACTS 和 ESO 指定专家的审查。

工作组的所有专家批准了经过适当修订后的指南。最终版本由 CPG、EACTS 和 ESO 批准,发表在欧洲心

脏杂志、欧洲起搏杂志、欧洲心胸外科杂志以及国际卒中杂志(TBC)上。本指南是在仔细考量了科学和

医学知识以及当下可提供的证据后制定的。

ESC 和 EACTS 制定指南的任务不仅涵盖了整合最新的研究,也包括教育工具和推荐措施实施方案的

创立。为实施这些指南,制作了简要的袖珍版指南、摘要幻灯片、基本信息的小册子、非专业人员的总结

卡片和数字应用(智能手机等)中的电子版。这些版本是删节版,因此如果需要的话,应当参考全文版,

这在 ESC 网站上免费提供。鼓励 ESC 国家各学会认可、翻译并执行所有的 ESC 指南。实施方案是必要

的,因为已证明全面应用临床推荐对疾病的转归具有有利的影响。

为验证真实世界中的日常实践与指南推荐是否一致,调查和注册研究是必要的,这样才能完成临床研

究、指南写作和传播,并应用于临床实践的循环。

鼓励健康专业人员在作出临床判断,包括临床决策,以及实施预防、诊断或治疗的医疗策略时,充分

考虑 ESC 和 EACTS 指南。然而,ESC 和 EACTS 指南不以任何方式凌驾于卫生专业人员的个人责任之

上,他们可在考虑到每个患者的健康状况,并与患者及其照顾者进行适当和/或必要的协商后,做出适当和

正确的决定。在处方时,核实适用于药品和设备的法律规章也是健康专业人员的责任。

2.前言

尽管在心房颤动(AF)患者的管理上取得了很好的进展,但这种心律失常仍然是世界范围内卒中、心

力衰竭、猝死和心血管死亡的主要原因之一。此外,预期在未来几年内 AF 患者的数量将明显增加。为了

满足 AF 患者有效医疗护理的日益增长的需要,新的信息不断产生并发表,近几年已经有了实质上的进

展。因此,发表第二版 ESC AF 指南看来是及时的。

为反映多学科投入 AF 患者的管理,工作组包括了不同亚专业的心脏病专家、心脏外科医师、卒中神

经病专家和护理专家。正如序言中所列出的,补充了证据审阅,工作组定义了与指南主题相关的三种人

群,干预,比较,结果,时间(PICOT)的问题。ESC 委托外部系统评价来回答这些问题,而这些评价已

经为特定推荐提供了资料。为进一步遵守所有 ESC 指南(见序言)共同的推荐标准,工作组在网络会议上

讨论了每项推荐草案,专门讨论了特定章节,然后对每项推荐进行共识修改和在线投票。仅有得到 75%以

上工作组成员支持的推荐才被纳入指南。

我们希望这些指南在最新的 2016 年的证据基础上,有助于对所有 AF 患者提供良好的管理。

3.流行病学和对患者的影响

3.1 心房颤动的发病率和患病率

在 2010 年,估计世界范围内 AF 的男性和女性分别为 2090 万和 1260 万人,在发达国家中发病率和患

病率更高[1,2]。在欧洲和美国每 4 名中年人中就有 1 名将发生 AF[3-5]。到 2030 年,预期在欧洲有 1400 万-

1700 万名 AF 患者,每年新诊断 12 万-21.5 万名患者[2,6,7]。估测表明在 20 岁或以上成人中 AF 的患病率约

为 3%[8,9],在老年患者以及合并其他疾病,如高血压、心力衰竭、冠状动脉性心脏病(CAD)、瓣膜性心

脏病、肥胖、糖尿病或慢性肾病(CKD)患者中患病率更高[7,10-15]。AF 患病率的增加可能是由于更多地检

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出了无症状的 AF [16-18],以及年龄增长和诱发 AF 的情况增加[19]。

3.2 心房颤动的致残致残率、死亡率和卫生保健负担

AF 与全因死亡风险女性增加 2 倍,男性增加 1.5 倍独立相关[20-22](表 3)。由于脑卒中导致的死亡在

很大程度上可通过抗凝治疗得以改善,而其他心血管死亡,例如心力衰竭和猝死,即使在根据近期指南进

行治疗的 AF 患者中仍然常见[23]。AF 也伴有致残率增加,如心力衰竭和卒中[21,24,25]。当今的研究表明有

20-30%的缺血性卒中患者在事件发生前、发生期间或发生后诊断了 AF[17,26,27]。脑白质损伤、认知功能障

碍[28-30],生活质量下降[31-32]和抑郁情绪在 AF 患者中常见,每年有 10-40%的 AF 患者入院治疗[23,34,35]。

在英国,AF 的直接花费已经占医疗保健支出总费用的大约 1%;2008 年,美国由 AF 相关并发症(如

卒中)和治疗产生的费用为 60-260 亿美元[36,37]。除非 AF 得到预防和及时有效的治疗,这些费用将显著增

加。

3.3 循证管理对心房颤动患者结局转归的影响

图 1 描述了 AF 管理中主要的里程碑式事件。尽管有这些进展,但仍保持很高的致残率。维生素 K 拮

抗剂类(VKAs)口服抗凝剂(OAC)或非 VKA 口服抗凝剂(NOACs)明显降低 AF 患者的卒中和死亡率[38,39]。其他干预措施如节律控制和室率控制改善 AF 相关症状,并可能保存心脏功能,但是未能证实减少

长期致残率或死亡率[40-41]。

表 3 与心房颤动相关的心血管发病率和死亡率

事件 与 AF 相关

死亡 死亡率增加,尤其是由于猝死、心力衰竭或卒中导致的心血管死亡

卒中

所有卒中的 20-30%是由于 AF 所致。卒中患者中诊断为无症状、阵发性 AF

的数量日益增加。

入院 每年有 10-40%的 AF 患者入院治疗。

生活质量 AF 患者的生活质量下降,独立于其他心血管疾病

LV 功能不全和

心力衰竭

20-30%的 AF 患者有左室功能不全。在许多 AF 患者中,AF 引起或加重 LV

功能不全,而其他患者尽管有长程持续性 AF,其 LV 功能得以保留。

认知功能下降

和血管性痴呆

即使在抗凝治疗的 AF 患者中,也可发生认知功能下降和血管性痴呆。与没

有 AF 的患者相比,AF 患者中脑白质病变很常见。

AF:心房颤动;LV:左心室。

在当前有良好对照的随机化 AF 临床试验中,在抗凝治疗的 AF 患者中,年平均卒中率大约为 1.5%,

每年的死亡率大约为 3%[40]。在真实世界中,年死亡率可能与此不同(可能较高或较低)[42]。这些死亡小

部分与卒中相关,而心源性猝死和由于心力衰竭进展所引起的死亡是常见的,这再次强调了需要除抗凝治

疗之外的干预措施[43,44]。此外,AF 与高入院率相关,通常是为治疗 AF,但也常常因为治疗心力衰竭、心

肌梗死以及治疗相关并发症[34,35]。

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3.4 性别

在发达国家和发展中国家,经年龄调整的 AF 的发病率和患病率在女性中均较低,而 AF 女性的死亡

风险与 AF 男性相似或较高[1,46,47]。具有额外卒中危险因素的女性 AF 患者(尤其是老年)比男性有更高的

卒中风险[48,49],即使在应用华法林抗凝的患者中也是如此[50](详见第 9 章)。诊断为 AF 的女性比男性可

能有更多的症状,通常年龄更大,有更多的合并疾病[51,52]。抗凝的出血风险两性相似[49,50,53],但是女性似

乎更少接受专业照顾和节律控制治疗[54],而导管消融或 AF 手术的效果与男性相当[55,56]。这些观察结果凸

显出对男性和女性需要同等地提供有效的诊断工具和治疗管理。

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与性别相关的推荐

推荐 推荐

类别

证据

水平

参考

文献

AF临床医师必须为女性患者提供与男性相同的有效诊断工具和治疗管

理措施,以预防卒中和死亡。 Ⅰ A

39,46,

57

导管或外科消融技术在女性和男性中同样有效。 Ⅱa B 55,56

AF:心房颤动。

4.指导管理的病理生理学和遗传因素

4.1 遗传倾向

AF,尤其是早发 AF,有强烈的遗传因素,独立于并发的心血管疾病[58,59]。一些年轻的 AF 患者,患

有遗传性心肌病或致病突变介导的离子通道病。这些单基因疾病还带来猝死风险(见第 6 章)。高达 1/3

的患者携带有易患 AF 的常见基因突变,尽管其附加风险相对较低。已知这些常见变异中的至少 14 种——

多是单核苷酸多态性——增加人群中的 AF 流行风险[60-62]。最重要的变异定位于邻近 4 号染色体长臂

(4q25)的对像同源结构域转录因子 2(Pitx2)基因处[63,64]。这些变异可使 AF 风险增高达 7 倍[64]。几种

AF 风险变异还与心源性栓塞或缺血性卒中相关,可能是由于隐匿性 AF 所致(见 4.1 节)[62,65,66]。心房动

作电位特征变化[67-70],心房重构和罕见基因修饰渗透缺陷均作为可能机制,介导常见基因变异携带者中

AF 风险的增加。在将来,基因变异可能对选择节律控制或室率控制的患者有用[71-74]。而且将来基因组分

析可能提供改善 AF 诊断和管理的机会[75,76],目前不推荐常规检测 AF 相关的常见基因变异[77]。

4.2 导致心房颤动的机制

4.2.1 心房结构重构和离子通道功能

外部应激源,例如结构性心脏病、高血压,可能还有糖尿病,而且 AF 本身也诱发缓慢而渐进性的心

房结构重构(图 2)。成纤维细胞激活、结缔组织沉积增多和纤维化是这一过程的标志[78-80]。此外,在合

并其他 AF 易患因素的 AF 患者中发现了心房脂肪浸润,炎症浸润、心肌细胞肥厚、坏死和淀粉样变性[81-

84]。结构重构导致肌束间的电分离和局部传导的不均一性[85],有利于折返和心律失常的维持[86]。许多患者

的结构重构进程发生在 AF 发作前 [78]。由于某些结构重构是不可逆的,故早期启动治疗似乎是理想的[87]。表 4 概述了与 AF 有关的心房组织中最相关的病理生理学改变,并列出了可能引起这些变化的相应的

临床情况。

心房肌的功能和结构改变和血液淤滞,尤其是在左心耳(LAA)部位,可产生促进血栓形成的环境。

此外,即使 AF 短期发作,也可导致心房肌损伤和心房内皮表面促血栓因子表达,血小板和炎症细胞激

活,并导致广泛的血栓前状态[88,89]。心房和全身凝血系统激活能够部分解释为何 AF 短期发作也会造成长

期卒中风险。

4.2.2 心房颤动的电生理机制

在心律失常的第一天,AF 促发心房不应期和 AF 周长缩短,大多是由于 Ca2+内流下调,以及内向整流

K+电流上调所致[94,95]。相反,结构性心脏病倾向于延长心房不应期,说明在不同的患者中引起 AF 机制的

异质性特征[96]。不同 Ca2+调控蛋白的高度磷酸化可能有助于增强自发性 Ca2+释放事件和触发活动[97,98],从

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而引起异位激动并促发 AF。尽管近来 Ca2+调控不稳定性的概念已经受到挑战[106,107],但它可能介导结构重

构心房中的 AF,这可解释为何自主神经张力改变能引起 AF[80,105]。

4.2.2.1 心房颤动的局灶启动和维持

Haissaguerre 等[108]进行的开创性观察提出肺静脉局灶起源可触发 AF,而消融这一起源可能抑制 AF 复

发。局灶活动的机制可能与触发活动和局部折返相关[109,110]。在阵发性 AF 患者中,已经记录到 AF 快速激

动区域的层级组织驱动心律失常[111,112],但是在未经选择的持续性 AF 患者中不明显[113]。

4.2.2.2 多子波假说和心房颤动的转子起源

Moe 和 Abildskov[114]提出了 AF 能得以延续,是由于几个独立子波通过心房肌组织以一种看似混乱的

方式而连续传播所致。只要波阵面的数量不降低至某一临界水平,它们就能使心律失常维持。大量的实验

和临床观察与多子波假说相一致[115]。AF 的所有局灶起源(异位激动灶、转子或其他稳定的折返环)都可

引起自源头起的颤动样传导,这很难与多个子波扩布维持的 AF 相鉴别,并且这种现象可能产生“转

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子”,可通过心内[116,117]或体表电极记录[117]到。

5.心房颤动的诊断和及时检出

5.1 显性和隐匿性心房颤动

AF 的诊断需要使用心电图(ECG)进行节律证实,显示典型的 AF 模式:RR 间期绝对不齐,没有可

分辨的 P 波。ECG 证实的 AF 是形成这些指南证据的 AF 的纳入标准。按照公认的惯例,发作持续至少 30

s 才能诊断。AF 患者可能有或没有症状(“隐匿性 AF”)。许多 AF 患者既可有症状性 AF 发作也可有

无症状性 AF 发作。

隐匿性,未检测到的 AF 是常见的[120,122],可致诸如卒中和死亡等严重后果[123-125]。即刻的 ECG 记录

是证实慢性 AF 的有效且性价比高的方法[126]。检测阵发性、自行终止的 AF 发作的技术正在迅速进展(见

6.1 章 AF 形式的定义)。有充分的证据表明,长时间的心电图监测可提高未诊断的 AF 的检出率,例如卒

中后监测 72 小时[27,127]甚至更长的时间[18,128]。每日短时间 ECG 记录可提高 75 岁以上人群的 AF 检出率[129]

(网页图 1)。正在进行的研究将明确这样的早期检测能否改变 AF 治疗(如启动抗凝)并改善转归。一

旦确定了 AF 的诊断,在以下情况需要进一步的 ECG 监测:(1)症状变化或有新发症状;(2)怀疑 AF

进展;(3)药物控制室率的效果监测;(4)抗心律失常药物或导管消融控制节律的效果监测。

5.2 隐匿性心房颤动的筛查

5.2.1 在社区通过心电图筛查心房颤动

未诊断的 AF 是常见的,尤其是在老年人群和有心力衰竭的患者中[130]。对于老年人群(如>65

岁),隐匿性 AF 的机会性筛查似乎具有高性价比[131],与已报道的在其他风险人群中使用单导联 ECG 筛

查具有同样的效果[132,133]。使用短期 ECG 或触诊脉搏的方法(对脉搏不规律的患者随后进行 ECG 检

查),在 122,571 名老年人(平均年龄 64 岁)中进行的筛查,得出慢性 AF 的患病率为 2.3%[134]。在年龄

>65 岁的老年人中,发现此前未诊断的 AF 为 1.4%,这表明查出 1 例 AF,需要筛查 70 人。这些发现鼓励

进一步评价在风险人群中进行系统性 AF 筛查的计划。

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表 4 心房颤动伴随的心房组织病理生理学变化和可能引起这些变化的临床情况

病理生理学变化 引起这些变化的临床情况 促心律失常机制/功能结果 参考

文献

细胞外基质、成纤维细胞功能和脂肪细胞变化

间质和纤维化替

AF(尤其是高 AF 负荷),高

血压,心力衰竭,瓣膜性心脏

病(通过压力和容量超负荷介

导)

电分离,传导阻滞,增加 AF 复

杂性

78,79,

90,91

炎症浸润 促纤维化反应,增加 AF 复杂性 81

脂肪浸润 肥胖 促纤维化/促炎症反应,局部传

导阻滞

82,92

淀粉样蛋白沉积 衰老,心力衰竭,冠心病(通

过心房瘢痕介导),遗传因素

传导紊乱 83,93

离子通道变化

离子通道重构 AF(尤其是高 AF 负荷),

AF 的遗传易感性

AF 周长缩短(如果由于房性心

动过速所致),AF 周长延长

(如果由于心力衰竭所致),

增加心房复极化的不均一性

94-96

Ca2+调控不稳定 AF(尤其是高 AF 负荷),心

力衰竭和高血压(可能通过增

加交感活性介导)

增加异位激动的倾向 97,98

缝隙连接再分布 AF 传导紊乱 99

心肌变化

细胞凋亡和坏死 冠心病,心力衰竭(通过心肌

细胞死亡和心房瘢痕介导)

可能诱发纤维替代 100

心肌细胞肥厚 心房扩大,AF 加重传导紊乱 84,101

内皮和血管变化

微血管变化 动脉粥样硬化,冠状动脉和外

周动脉疾病,可能心房颤动

加重心房缺血,电功能的不均

一性,结构重构

102

内皮重构 增加血栓形成风险 103,104

自主神经系统变化

交感神经过度再

心力衰竭,高血压 增加异位激动倾向 80,105

AF:心房颤动;CAD:冠心病。

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5.2.2 阵发性心房颤动的延长监测

阵发性 AF 经常被漏诊[120]。在>75 岁未经选择的瑞典人群中,重复每日 ECG 记录,提高了隐匿性无

症状阵发性 AF 的检出率[120,135]。已证实几种患者操作的器械[136,137]和长期的使用皮肤贴片记录的持续 ECG

监测仪[138]对阵发性 AF 的检出有效(网页图 1)[139]。通过新技术如带有 ECG 电极的智能电话,智能手表

和带有 AF 检测算法的血压记录仪等来检测无症状的 AF,仍未得到正式评估,不能作为确切的心律失常检

测方法[140]。

5.2.3 带有起搏器和植入性器械的患者

带有心房导线的植入式起搏器或除颤器允许进行持续的心房节律监测。使用这一技术,能检出患者的

心房高频事件(AHRE)。根据人群研究的风险水平,起搏器患者中有 10-15%能够检测到这种

AHRE[141]。AHRE 与显性 AF 风险[风险比(HR)5.56,95%可信限(CI)3.78-8.17,P<0.001] 和缺血性

卒中或系统性栓塞风险(HR2.49;95%CI1.29-4.85;P=0.007)增高相关。在 AHRE 患者中,卒中风险似

乎低于已确诊的 AF 患者,不是所有的 AHRE 均代表 AF[142]。卒中通常发生于在事件发生前 30 天内没有

检测到 AHRE 的患者中[143-147]。因此,尚不清楚 AHRE 是否像显性 AF 那样需要治疗[148]。正在进行临床试

验来验证在 AHRE 患者中 OAC 治疗的获益[如,阿哌沙班降低器械检出亚临床心房颤动患者的血栓栓塞风

险(ARTESiA)(NCT01938248),和非维生素 K 拮抗剂类口服抗凝剂治疗心房高频事件患者(NOAH-

AFNET6)(NCT02618577)]。当前,应定期询问起搏器和植入性器械记录的 AHRE 情况,AHRE 患者应

当接受进一步的卒中风险因素和显性 AF 的评估,包括 ECG 监测(图 3)[149]。

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5.2.4 卒中幸存者中心房颤动的检出

一系列的分层 ECG 监测在 24%(95%CI 17-31)的卒中幸存者中检测出了 AF[151],在另一项荟萃分析中

可检出 11.5%(95%CI 8.9%-14.3%)[17],这种较大的变异取决于检测时机、持续时间和检测方法。在未经选

择的卒中患者中,检出 AF 并非少见(6.2%,95%CI 4.4-8.3)[128],但在植入了循环记录仪的隐源性卒中患

者或 ECG 监测数周的患者中,检出率则更高 [18,128,152]。隐源性卒中定义是:在广泛调查后,病因仍未被确

定的卒中[153]。广义而言,是未明确来源的血栓性卒中[154]。几项研究还发现在某些 AF 患者中,在临床上识

别了其他的竞争性病因(如高血压或颈动脉狭窄)[27,127]。因此,在所有没有确定 AF 的缺血性卒中幸存者

中,延长 ECG 监测似乎是合理的。

5.3 心房扑动的心电图检测

右心房峡部依赖性心房扑动表现为典型的 ECG 形态和心室率[158]。心房扑动的患病率不到 AF 患病率的

1/10[159]。心房扑动经常与 AF 共存或在 AF 之前发生[160]。典型的峡部依赖性心房扑动,P 波通常显示为“锯

齿”形,尤其是在下壁导联(Ⅱ、Ⅲ、avF)上。心室率可能有变化(通常心房至心室的传导比例为 4:1 至

2:1,罕见病例为 1:1),而在稳定的 2:1 传导时,可能会错过大折返性心动过速。迷走神经刺激或静脉注射

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腺苷可能有助于揭示心房扑动。在 12.7 节中讨论了心房扑动的治疗。左房或右房大折返性心动过速主要见

于 AF 导管消融后、AF 外科手术或开胸心脏手术后的患者中 [158]。

心房颤动筛查的推荐

推荐 推荐

类别

证据

水平

参考

文献

推荐对于>65 岁的患者,通过触诊脉搏或 ECG 节律记录条图进行

机会性筛查。

Ⅰ B 130,134,

155

对于 TIA 或缺血性卒中患者,推荐短期 ECG 记录后,进行连续心

电图监测至少 72 小时筛查 AF。

Ⅰ B 27,127

推荐定期询问起搏器和 ICD 记录的心房高频事件(AHRE)。AHRE

患者应当接受进一步的 ECG 监测,以在启动 AF 治疗前获得 AF 记

录。

Ⅰ B 141,156

在卒中患者中,应考虑通过长程非侵入性 ECG 监测或植入式循环记

录仪进行额外的 ECG 监测,以记录隐匿性心房颤动。

Ⅱa B 18,128

对于年龄>75 岁的患者或存在卒中高风险的患者,可以考虑进行系

统的 ECG 筛查以检出 AF

Ⅱb B 130,135,

157

AF:心房颤动;AHRE:心房高频事件;ECG:心电图;ICD:植入式心律转复除颤器;TIA:短暂性脑缺血发

作。

6.心房颤动的分类

6.1 心房颤动类型

在许多患者中,AF 从短时间、不常发作进展到较长时间和频繁发作。随时间推移,许多患者将发展为

持续性 AF。在小部分 AF 患者(2-3%)中,AF 将在几十年里保持为阵发性 [161]。阵发性 AF 复发的分布不

是随机的,而是呈簇状分布[162]。AF 也可从持续性退回到阵发性。此外,在有症状的 AF 患者中,AF 的无

症状性复发常见[120]。

根据 AF 发作的临床表现、持续时间和是否自发终止,传统上将 AF 分为 5 种类型:首次诊断的、阵

发性、持续性、长程持续性和永久性 AF(表 5)。如果患者既存在阵发性也存在持续性 AF 发作,应当按

照其更常见的类型进行分类。临床确定的 AF 类型与通过长时间 ECG 监测测定的 AF 负荷并不能很好相关[163]。甚至对于长程持续性 AF 或长期阵发性 AF 的患者的治疗反应所知更少。尽管这不够精确,但阵发性

和持续性 AF 之间的区别一直在许多试验中使用,因此,仍形成了这些推荐的基础。

有证据表明 AF 负荷可能影响卒中风险[44,124,164],可能影响对节律控制药物的反应 [76,165],但这些证据

较弱。因此,AF 负荷不能作为确定因其他原因使用某项干预措施有用性的主要因素。

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表 5 心房颤动的类型

AF 形式 定义

首次诊断的 AF 之前未曾诊断过 AF,无论心律失常持续时间或是否存在 AF 相关症状

及其严重程度

阵发性 AF 自行终止,大多数病例在 48 小时以内终止。一些患者阵发性发作可能

持续至 7 天 a。在 7 天内被复律的 AF 发作应视为阵发性的 a。

持续性 AF 持续长于 7 天的 AF,包括在 7 天或更长时间后通过复律终止的发作,

无论是用药物还是通过直流电复律。

长程持续性 AF 当决定采用节律控制策略时,持续≥1 年的连续性 AF。

永久性 AF 已经被患者(和医生)接受的 AF。因此,根据定义,对于永久性 AF

患者,并不追求节律控制治疗。一旦采用节律控制策略,这种心律失常

就应重新被分类为“长程持续性 AF”。

AF:心房颤动

a:在没有进行长时间监测的情况下,阵发性和持续性 AF 之间通常不能做出正确的辨别[163]。因此,单凭这一分类

来选择特异性治疗通常是不够的。如果持续性和阵发性发作均存在,应当用主要的发作形式指导分类。

6.2 反映不同的心律失常病因的心房颤动类型

多种生理和疾病状态下发生 AF 的风险增加(图 2),曾应用的术语“孤立性 AF”可能会产生误导,

应当避免[166]。尽管 AF 的类型可能是相同的,但 AF 的基本机制在不同患者间有着根本性的不同[167](表

6)。这表明根据 AF 潜在的驱动因素对 AF 患者进行分层可能指导治疗,例如,要考虑心脏和全身性疾病

(如糖尿病和肥胖[168]),生活方式因素(例如活动水平、吸烟、酒精摄入[169,170]),心脏结构重构的标志

(如纤维化[171-173]或 AF 复杂性的心电图参数[174]),或遗传背景。表 6 提供了这种专家共识分类[76,120,175],

但是没有更多的证据支持其在临床上的应用[176]。显然需要系统性研究确定 AF 的主要驱动因素,以更好地

定义不同的 AF 类型[176]。

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表 6 心房颤动的临床类型

AF 类型 临床表现 可能的病理生理学改变

继发于结构性

心脏病的 AF

LV 收缩或舒张功能不全、长期高

血压伴有 LVH 和/或其他结构性心

脏病患者中的 AF。这些患者中 AF

发作是住院的常见原因和不良预后

的预测因子。

心房压力增加,心房结构重构,伴有交感

神经和肾素-血管紧张素系统激活。

局灶性 AF 具有反复和频繁的心房激动,阵发

性心房颤动短期发作的患者。通常

症状明显、较年轻,伴有可识别的

心房波(粗颤),心房异位激动和

/或房性心动过速恶化为 AF。

在大多数患者源于肺静脉的局灶触

发因子诱发的 AF。

由一个或几个折返驱动灶引起的 AF 也

被认为是这类 AF 的一部分。

多基因 AF 伴有早发房颤常见基因变异携带者

的 AF。

目前仍在研究。选择性基因变异的存在

可能也影响治疗效果。

术后 AF 术前为窦性心律,既往无 AF 史的

患者,在重大(尤其是心脏)外科

手术后新发的 AF(通常可自行终

止)。

急性因素:炎症、心房氧化应激、交感活

性增高、电解质变化和容量超负荷,可能

与原先存在的基质间存在交互作用。

二尖瓣狭窄或

机械瓣膜患者

的 AF

二尖瓣狭窄患者、二尖瓣外科手术

后和某些情况下其他瓣膜疾病患者

的 AF。

这些患者中左心房压力(狭窄)和容量

(返流)负荷是心房扩大和心房结构重

构的主要驱动因素。

运动员 AF 通常呈阵发性,与训练的持续时间

和强度有关。

迷走神经张力和心房容量增加。

单基因 AF 遗传性心肌病,包括离子通道病患

者中的 AF。

在这些患者中,引起猝死的致心律失常

机制有可能有利于 AF 的发生。

AF:心房颤动;CAD:冠心病。

6.3 心房颤动的症状负荷

AF 患者的生活质量明显不如健康对照者,会产生不同的症状,包括倦怠、心悸、呼吸困难、胸闷、

入睡困难和心理困扰[32,177-180]。已注意到药物和介入治疗均可改善生活质量[181-185],但是比较不同治疗获益

的数据有限[32,186]。几个 AF 特异性生活质量评价工具之间缺乏交叉验证,使生活质量的评价受到限制[187-

191]。对于症状评估,EHRA 建议使用 EHRA 症状评分 (表 7)描述 AF 患者中症状的严重性[192]。在加拿

大使用相似的评分(加拿大心血管协会心房颤动症状评分)[193]。EHRA 评分一直在使用,并确认有效[194-

199]。在 2014 年提出了一项修改意见,将 EHRA 2 级细分为轻度(2a 级)或中度(2b 级)[199]。由于在这

项研究中,症状为 2b 级(“困扰的”症状)的患者可从节律控制中获益,这一修改可能为潜在的治疗决

策提供一种阈值,但有待于独立进行验证。尽管一些 AF 患者(25-40%)没有或只有轻微症状,而一些患

者(15-30%)诉有严重或致残性症状[194,196]。改良的 EHRA 评分应当用于指导症状为导向的治疗决策,以

及对患者进行纵向的症状分析。

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表 7 改良的欧洲心律协会症状标准(根据 Wynn 等的分类修改[199])

AF 类型 临床表现 可能的病理生理学改变

1 无 AF 不引起任何症状

2a 轻度 正常日常活动不受 AF 相关症状的影响 a

2b 中度 正常日常活动不受 AF 相关症状的影响,

但是患者受到症状困扰 a。

3 严重 正常日常活动受到 AF 相关症状的影响

4 致残 正常日常活动终止

AF:心房颤动;EHRA:欧洲心律协会;

a:EHRA 2a 级和 2b 级可通过评估其 AF 症状是否影响患者功能进行鉴别。最常见的 AF 相关症状有疲乏/疲劳、劳

力性呼吸困难,或不太常见的心悸和胸痛。

关于使用改良的欧洲心律学会症状标准的推荐

推荐 推荐

类别

证据

水平

参考

文献

推荐在临床实践中和定量 AF 相关症状的研究中使用改良的 EHRA

症状标准 Ⅰ C 192,199

AF:心房颤动;EHRA:欧洲心律协会。

7.危险因素和伴随的心血管疾病的检出和管理

许多心血管疾病和伴随疾病可使 AF 的发生(表 8)、复发以及 AF 相关并发症的风险增高。这类情况

的识别及其防治,是预防 AF 及其疾病负担的重要手段。因此,掌握这些因素及其管理知识,对优化 AF

患者的管理是很重要的[203,204]。

7.1 心力衰竭

在许多患者中,心力衰竭和 AF 共存[215-217]。它们具有相似的危险因素和共同的病理生理特征[218]。通

过诸如心脏结构重构、神经内分泌激活机制以及频率相关的左心室(LV)功能受损等机制,心力衰竭和

AF 可互为因果,并互相加重。AF 合并心力衰竭的患者,包括射血分数保留(LVEF)≥50%]和射血分数

降低(LVEF<40%)的患者[219,220],预后不良,包括死亡率增加[16,221]。最近的 ESC 心力衰竭指南[222]还引

入了一类射血分数中间值的心力衰竭(HFmrEF,LVEF40-49%),但在这个组中 AF 患者的数据有限。对

不良结局的预防和维持良好的生活质量是所有 AF 合并心力衰竭患者的管理目标。无论其 LVEF 水平如何[223]。AF 管理的一般方法在心力衰竭患者和其他患者之间并无差异,但是有些考虑是有价值的。值得注意

的是,这些患者中被证实有预后价值的仅有抗凝治疗,对于所有存在卒中风险的患者,都应当处方适宜的

OAC(见第 8 章)。

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表 8 与心房颤动独立相关的心血管和其他疾病

与 AF 相关性 特征/共病

遗传倾向(基于与 AF 相关的多个常见基因变异) HR 范围 0.4-3.2

老年[19]

50-59 岁

60-69 岁

70-79 岁

80-89 岁

HR:

1.00(参照)

4.98 (95% CI 3.49–7.10)

7.35 (95% CI 5.28–10.2)

9.33 (95% CI 6.68–13.0)

高血压(治疗)vs.无高血压[19] HR 1.32 (95% CI 1.08–1.60)

心力衰竭 vs.无心力衰竭[19] HR 1.43 (95% CI 0.85–2.40)

瓣膜性心脏病 vs.无瓣膜性心脏病[205] RR 2.42 (95% CI 1.62–3.60)

心肌梗死 vs.无心肌梗死[19] HR 1.46 (95% CI 1.07–1.98)

甲状腺功能异常[206,207]

甲状腺功能减退

亚临床甲状腺功能亢进

显性甲状腺功能亢进

(参照:正常甲功)

HR 1.23 (95% CI 0.77–1.97)

RR 1.31 (95% CI 1.19–1.44)

RR 1.42 (95% CI 1.22–1.63)

肥胖[19,208]

无(BMI<25kg/m2)

超重(BMI<25-30kg/m2)

肥胖(BMI≥31kg/m2)

HR:

1.00 (参照)

1.13 (95% CI 0.87–1.46)

1.37 (95% CI 1.05–1.78)

糖尿病 vs.无糖尿病[19] HR 1.25 (95% CI 0.98–1.60)

慢性阻塞性肺疾病[209]

FEV1 ≥80%

FEV1 60-80%

FEV1<60%

RR:

1.00 (参照)

1.28 (95% CI 0.79–2.06)

2.53 (95% CI 1.45–4.42)

阻塞性睡眠呼吸暂停 vs.无[210] HR 2.18 (95% CI 1.34–3.54)

慢性肾病[211]

1 或 2 期

3 期

4 或 5 期

OR:

1.00 (参照)

2.67 (95% CI 2.04–3.48)

1.68 (95% CI 1.26–2.24)

3.52 (95% CI 1.73–7.15)

吸烟[212]

从不吸烟

以前吸烟

当前吸烟

HR:

1.00 (参照)

1.32 (95% CI 1.10–1.57)

2.05 (95% CI 1.71–2.47)

饮酒[213]

不饮酒

1-6 份/周

7-14 份/周

15-21 份/周

>21 份/周

RR:

1.00 (参照)

1.01 (95% CI 0.94–1.09)

1.07 (95% CI 0.98–1.17)

1.14 (95% CI 1.01–1.28)

1.39 (95% CI 1.22–1.58)

AF:心房颤动;BMI:体重指数;CI:可信限;FEV1:1 秒用力呼吸量;HR:风险比;OR:比数

比;RR:危险比。

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7.1.1 伴有射血分数降低的心力衰竭的心房颤动患者

除了 OAC 外,标准的心力衰竭治疗应当用于伴有射血分数降低的心力衰竭患者(HFrEF),详见

ESC 指南[222]。这包括血管紧张素转换酶(ACE)抑制剂或血管紧张素受体拮抗剂(ARBs),醛固酮拮抗

剂、除颤器、心脏再同步化治疗[218],以及在能够耐受 ACE 抑制剂或 ARBs、有持续症状的患者中使用血

管紧张素/脑啡肽酶抑制剂(ARNI)治疗[224]。

AF 的节律控制在第 9 章进行了讨论。简短来说,仅仅β阻滞剂和地高辛适用于 HFrEF,因为维拉帕

米和地尔硫卓均有潜在的负性肌力作用。β阻滞剂在临床稳定的 HFrEF 患者中通常作为一线选择,但应用

来自于随机化对照试验(RCTs)中个体患者数据的荟萃分析发现在基线存在 AF 的患者中,β阻滞剂与安

慰剂相比没有降低死亡率(HR 0.97, 95% CI 0.83–1.14)[23]。在临床实践中经常处方地高辛,但是没有在

AF 患者中进行头对头的 RCT。在观察性研究的荟萃分析中,地高辛对 AF 合并心力衰竭患者的死亡率是

中性效应(经调整的观察性研究 HR 0.90, 95% CI 0.70–1.16,倾向性匹配的观察性研究 RR 1.08,95% CI

0.93–1.26)[225]。因此,在 HFrEF 患者中启动和联合室率控制治疗时,应当考虑到患者的个体特征和症

状;在急性失代偿性心力衰竭的患者中,应推迟β阻滞剂的使用,在肾功能不全的患者中,地高辛可蓄

积,从而诱发不良反应(见第 9 章)。

存在严重症状的 AF 合并 HFrEF 的患者可能除了室率控制治疗外,需要节律控制治疗。对由于快速

AF 引起 HFrEF 的患者(心动过速性心肌病),首选节律控制策略,几个相对小规模的患者队列和研究报

告在恢复窦性节律后改善 LV 功能[185,226-228]。心动过速心肌病的诊断可能是个挑战,有时需要在恢复窦性

节律后作出[229]。导管消融可能是恢复 AF 伴有 HFrEF 患者的 LV 功能和生活质量的有用方法[185,226-228],但

是仍需更多的数据。图 4 总结了 AF 合并心力衰竭患者的管理措施。

7.1.2 伴有射血分数保留的心力衰竭的心房颤动患者

在 AF 患者中诊断射血分数保留的心力衰竭(HFpEF)是存在问题的,因为很难分清楚症状是由于 HF

还是由于 AF 所致。尽管诊断鉴别可以通过心脏复律和再次临床评估达到目的,但是在当前缺乏 HFpEF 中

改善预后的措施情况下,改善症状应当作为特定的治疗。超声心动图能够通过提供相关结构性心脏病的证

据[如 LV 肥厚(LVH)]和/或对舒张性心功能不全的测量,检出症状性 AF 患者中的 HFpEF。组织多普勒

测定的舒张早期心肌速率 e’降低反映了 LV 松弛功能受损,而 E/e’比值与侵入性测定的 LV 充盈压相关[230-

234]。钠尿肽水平是 HFpEF 诊断性评估的一部分[222],但钠尿肽水平在 AF 患者中也增高,且其最佳诊断界

值仍然未知[235]。AF 合并 HFpEF 患者的管理应当关注液体平衡的控制以及合并的疾病,如高血压和心肌

缺血。

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7.1.3 伴有射血分数中间值的心力衰竭的心房颤动患者

HFmrEF 是最近定义的,描述了有心力衰竭的症状和体征,LVEF 40-49%,钠尿肽水平增高,并有 LV

肥厚,左房(LA)扩大或舒张性心功能不全证据的患者[222]。然而,在 AF 患者中其诊断更为困难,因为

钠尿肽在 AF 和 LA 扩张的患者中增高是常见的,无论其是否合并心力衰竭。在 AF 患者中,LVEF 易变且

难于评价,因为 AF 诱发收缩性 LV 功能降低,且心脏周长发生变化。在对 AF 合并 HFmrEF 的患者推荐特

殊治疗策略前,对这一组患者需要进一步研究。

7.1.4 心力衰竭患者中心房颤动的预防

来自大型随机化试验的回顾性分析,与安慰剂相比,应用 ACE 阻滞剂/ARBs 治疗的患者中新发 AF 的

发生率较低[236-238]。在 HFpEF 患者中,ACE 阻滞剂/ARBs 降低 AF 发生率的证据较少,在无心力衰竭的患

者中没有这方面证据[240-242]。脑啡肽酶抑制剂似乎没有这一额外效应[224]。在已应用 ACE 抑制剂/ARBs 治

疗的 HFrEF 患者中,β阻滞剂治疗可降低调整后的 AF 发生率 33%,这强调了在窦性心律的 HFrEF 患者

中β阻滞剂治疗的重要性[23]。依普利酮,一种盐皮质激素受体拮抗剂,对于 LVEF≤35%、 纽约心脏病学

会(NYHA)分级Ⅱ级的患者,在 ACE 抑制剂/ARBs 及β阻滞剂的基础上加用,也可降低新发 AF 风险

[243]。

7.2 高血压

高血压是 AF 卒中的危险因素;未控制的高血压增加卒中和出血事件的风险,可能导致 AF 复发。因

此,良好的血压控制应当成为 AF 患者管理不可或缺的一部分[247]。抑制肾素-血管紧张素-醛固酮系统可以

预防结构重构和 AF 复发[236,244]。最近,对丹麦健康数据库长期监测不同降压药物对显性 AF 发生的影响的

分析显示,ACE 抑制剂或 ARBs 可能有益[245]。对 ACE 抑制剂或 ARBs 在心力衰竭或 LVH 患者中进行的

二次分析显示新发 AF 较少 [238,246]。在已确诊 AF 但是没有 LV 功能不全或心力衰竭的患者,ARBs 预防

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AF 复发的效果不优于安慰剂[240,241]。与单独应用抗心律失常药物相比,同时应用抗心律失常药物和 ACE

抑制剂或 ARBs 可能减少复律后 AF 复发[248,249]。对这些研究进行的荟萃分析表明 AF 复发风险较低,但是

至少一项对照研究未能证实这一获益[240,251]。

7.3 瓣膜性心脏病

瓣膜性心脏病与 AF 发生独立相关[252]。大约 30%的 AF 患者有某种形式的瓣膜性心脏病,通常仅能通

过超声检出[201,253-255]。AF 使严重瓣膜性心脏病患者的预后恶化[256],包括那些接受外科或经导管介入治疗

主动脉瓣或二尖瓣疾病的患者[257-262]。瓣膜性心脏病伴有血栓栓塞风险增加,这可能也增加了 AF 患者的

卒中风险[263]。与心力衰竭相似,瓣膜性心脏病和 AF 相互作用,并通过容量和压力超负荷、心动过速性心

肌病和神经内分泌因素相互维持[264-270]。当严重瓣膜功能不全时,AF 被认为是疾病进展的标志,因此需要

瓣膜修复或置换[271]。

按惯例,AF 患者被分为“瓣膜性”和“非瓣膜性”AF[272]。尽管使用的定义有些不同,瓣膜性 AF 主

要指有风湿性瓣膜病(主要是二尖瓣狭窄)或置入了机械心脏瓣膜的 AF 患者。实际上,虽然在二尖瓣狭

窄的患者中,AF 意味着血栓栓塞风险的增加[263,273,274],但目前还没有明确证据表明,在 AF 选择抗凝治疗

或评估卒中风险时,需要考虑其他瓣膜疾病,包括二尖瓣返流或主动脉瓣疾病[275]。因此,我们已经决定更

改“非瓣膜性”AF 这一历史术语,而参考具体的基本情况。

瓣膜性心脏病合并心房颤动患者的推荐

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对于严重二尖瓣返流,LV 功能保留合并新发 AF 的患者,即使没有

症状,也应考虑早期二尖瓣手术,尤其是当瓣膜修复可行时。

Ⅱa C 276

对于无症状的严重二尖瓣狭窄,瓣膜解剖形态适宜的新发 AF 患者,

应考虑二尖瓣瓣膜成形术。

Ⅱa C

AF:心房颤动;LV:左心室。

7.4 糖尿病

因为有共同的其他危险因素,糖尿病和 AF 经常共存[277-283]。糖尿病是卒中和 AF 其他并发症的危险因

素[284]。在 AF 患者中,长期糖尿病可致血栓栓塞的风险增高,虽然不增加 OAC 相关出血风险[285]。不幸的

是,积极的血糖控制不影响新发 AF 的发生率[284],然而二甲双胍治疗似乎与糖尿病患者长期 AF 风险降低

相关[286],甚至可能与长期卒中风险降低相关[13]。糖尿病视网膜病变,是疾病严重性的指标,不增加抗凝

患者中眼部出血的风险[287]。

7.5 肥胖和减肥

7.5.1 肥胖是一种危险因素

肥胖增加 AF 风险(表 8)[288-291],并随着体质指数(BMI)增加而增加[288,290-292]。肥胖患者的舒张功

能可能更差,交感活性和炎症水平更高,以及心房脂肪浸润增加[293-295]。肥胖还可能是 AF 患者缺血性卒

中、血栓栓塞和死亡的危险因素[292]。

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对肥胖的心房颤动患者的推荐

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文献

在肥胖的 AF 患者中,应当考虑同时降低体重与管理其他危险因素,

以减轻 AF 负荷及症状。 Ⅱa B 204,288

,296

AF:心房颤动;LV:左心室。

7.5.2 肥胖心房颤动患者的减肥

对于肥胖的 AF 患者,除了管理其他心血管危险因素之外,相较于基于一般性推荐的方法,强化减肥

(减轻体重达到 10-15kg 的范围)可使 AF 复发减少且症状较少[203,204,296]。改善心肺适应能力可进一步降低

肥胖 AF 患者中的 AF 负荷[297]。尽管这些研究结果尚需证实,但其支持减轻体重对肥胖 AF 患者的积极影

响。

7.5.3 肥胖患者的导管消融

肥胖可能增加导管消融后 AF 的复发率[298-301],其中阻塞型睡眠呼吸暂停(OSA)是重要的潜在因

素。肥胖还与 AF 消融时需用较高的辐射剂量和并发症发生率相关[302,303]。值得注意的是,肥胖患者导管消

融 AF 后症状的改善似乎与正常体重患者相当[298]。鉴于减肥可减少 AF 发作(见 6.5.2 节),对于消融治

疗的肥胖 AF 患者,应同时建议其进行减轻体重的生活方式改变。

7.6 慢性阻塞性肺疾病,睡眠呼吸暂停和其他呼吸道疾病

AF 伴有阻塞性睡眠呼吸暂停[304,305]。多种病理生理机制可能有助于睡眠呼吸暂停患者发生 AF,包括

自主神经功能障碍,低氧血症,高碳酸血症和炎症[96,304-307]。阻塞性睡眠呼吸暂停使胸内压增大,其本身

以及通过迷走神经活动可促发心房动作电位缩短并诱发 AF。减少危险因素以及持续气道正压通气可减少

AF 复发[308-312]。在伴有危险因素的 AF 患者中,考虑进行阻塞性睡眠呼吸暂停的筛查看来是合理的。应对

阻塞性睡眠呼吸暂停的治疗进行优化,以改善 AF 的治疗结果。伺服控制压力支持治疗对以中枢性呼吸睡

眠暂停为主的 HFrEF 患者(其中 25%合并 AF)是无用的[313]。

慢性阻塞性肺疾病(COPD)患者通常有房性心动过速,在 ECG 上需要同 AF 鉴别。用于缓解支气管

痉挛的药物,特别是茶碱和β肾上腺素能受体激动剂,可能促发房颤,并使心室率难以控制。非选择性β

受体阻滞剂、索他洛尔、普罗帕酮和腺苷在有明显支气管痉挛的患者中应慎用,但其可安全地用于 COPD

患者。选择性β1 阻滞剂(例如比索洛尔、美托洛尔和奈必洛尔)、地尔硫卓和维拉帕米通常可耐受并且

有效(见第 9 章)。

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对心房颤动合并呼吸道疾病患者的推荐

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文献

对于急性肺疾病或慢性肺疾病恶化期间发生 AF 的患者,应考虑纠

正低氧血症和酸中毒作为初始治疗。 Ⅱa C

在所有 AF 患者中,应当考虑询问阻塞性睡眠呼吸暂停的临床表现 Ⅱa B

304,305,

314,315

应优化阻塞性睡眠呼吸暂停的治疗,以减少 AF 复发,改善 AF 治

疗效果 Ⅱa B

307-311

AF:心房颤动;LV:左心室。

7.7 慢性肾脏病

在 15-20%的慢性肾脏病(CKD)患者中存在 AF[316]。大多数 AF 试验中 CKD 的定义是相对严格的。

尽管估测的肌酐清除率(CrCl)<60mL/min 是 CKD 的标准,但在许多试验中,AF 患者使用 CrCl<

50mL/min 的标准调节 NOAC 剂量,通常使用 Cockroft-Gault 公式估测。AF 患者的 CrCl 可能随时间而恶化[317]。在伴有 CKD 患者中的 OAC 治疗在 8.2.4 节中讨论。

对心房颤动合并肾脏疾病患者的推荐

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文献

推荐对所有 AF 患者,通过血清肌酐或肌酐清除率评价肾功能,以

检出肾脏疾病,并为调整 AF 治疗药物的剂量提供依据。 Ⅰ A 316,318

-321

所有口服抗凝剂治疗的 AF 患者,均应当考虑至少每年评估一次肾

功能,以检出慢性肾脏疾病。 Ⅱa B

AF:心房颤动。

8.心房颤动患者的整体管理

大多数患者最初通过药剂师,社区卫生工作者,或初级保健医生接触医疗保健系统。由于 AF 经常没

有症状(“隐匿性 AF”),这些医护人员是使 AF 得到充分检出和确保一致管理的重要责任者。在第一次

接触医疗保健系统时,应当进行初始评估,这在大多数医疗保健环境中是可行的(当可提供 ECG 时)。

我们建议在对新诊断的 AF 患者进行初始评估时,要考虑如下 5 个方面(图 5):

(1) 血流动力学不稳定或受限,有严重的症状;

(2) 存在诱发因素(如甲状腺毒症、脓毒血症或术后 AF)和潜在的心血管疾病;

(3) 卒中风险和抗凝治疗需求;

(4) 心率和室率控制需求;

(5) 症状评估和确定节律控制。

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表 9 需要呼叫专业心房颤动服务紧急参与的临床征象 a

临床情况

血流动力学不稳定

心率无法控制

症状性心动过缓,减少心率控制药物无效

严重的心绞痛或左心室功能恶化

短暂性脑缺血发作或卒中

a:在所有适合的患者中应早期启动抗凝治疗,不需要专家常规介入。

AF 医疗护理中所应用的一体化结构化的方法,已在医疗的其他主要领域成功应用[322-324],这将有利于

在所有患者中进行一致的、符合指南的 AF 管理[325](图 6),并可能改善结局[42,326,327]。这一方法是与世

界卫生组织提出的慢性疾病创新照护框架的建议是一致的[328]。通常在初步评估后,常需要对 AF 服务进行

回顾,或至少转诊至心脏病专家处,以充分评估 AF 对心血管健康的影响[329]。这可能也是早期或急诊转诊

的原因(表 9)。所有新诊断 AF 患者的整体照护应当有助于克服近来 AF 管理的不足之处,如抗凝药物使

用不足,进行室率和节律控制治疗,以及降低心血管风险方法不一致等。整体 AF 照护需要初级医疗保健

医师、心血管专家、心外科医师、AF 专家、卒中专家合作,并联合健康从业人员和患者,包括生活方式

干预、潜在心血管疾病治疗以及 AF 特异性治疗(图 7)。

AF 的整体管理 AF 的整体管理 AF 的整体管理 AF 的整体管理

患者参与 多学科团队 技术工具 AF 获得所有最佳治疗

在照护过程中

起核心作用

患者教育

鼓励和激励自

我管理

生活方式和危

险因素管理的

建议和教育

共同决策

医师(全科医师、心

脏病和卒中 AF 专

家、外科医师),联

合健康从业人员以合

作的实践模式工作

沟通技巧、教育和经

验的有效融合

AF 信息

临床决策支持

表单和交流工具

健康从业者和患者使

治疗依从性和效果监

生活方式改变的结

构性支持

抗凝治疗

心率控制

抗心律失常药物

导管和外科干预

(消融,LAA 封

堵,AF 外科治疗

等)

知情、参与、

激励患者

多学科慢性 AF 管理

团队共同工作

支持治疗团队决策的

导航系统

基于 AF 心脏团队

的复杂的管理决策

AF:心房颤动;LAA:左心耳

图 7:心房颤动患者整体照护的基础

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8.1 支持心房颤动整体照护的证据

已经开发了 AF 结构性照护的几种方法。一些证据支持其应用,然而仍需要更多的研究为 AF 的一体

化管理提供最佳方式。一项 RCT 报道,在一家大型三级医疗中心,综合的 AF 管理提高了循证治疗的使

用,平均随访 22 个月,与常规照护相比,心血管住院和心血管死亡的复合终点约降低了 1/3(14.3% vs.

20.8%, HR 0.65;95% CI,0.45–0.93; P = 0.017)[330]。在这一研究中,AF 的整体管理显示有良好的成

本-效益比[331]。然而,一项澳大利亚的 RCT 显示,使用整体的 AF 管理,对非计划入院和死亡仅有临界效

果,且限于最初的治疗期,可能强调对 AF 需要坚持进行整体管理[332]。两项对 AF 整体管理的观察性研究

显示卒中病例较少[333],一项进一步非随机化研究发现死亡、心血管住院和 AF 相关的急诊复合终点率有降

低的趋势[335]。尚需要更多的研究,整体 AF 管理在不同的医疗环境中似乎需要不同的设计。

8.2 心房颤动整体照护的组成部分

8.2.1 患者参与

在医疗过程中,患者应当起到核心作用。因为 AF 的治疗需要患者改变他们的生活方式,并依从长期治

疗,在没有立即获益时,他们需要理解自己在医疗过程中的责任。医师和健康从业人员负责提供以证据为

基础的治疗,但是对治疗的坚持最终是知情和自主的患者的责任,最好的描述是“共同责任”[336]。这

样,患者经常还包括其伴侣和亲属进行告知和教育是必不可少的,以鼓励患者自我管理和允许患者参与共

同决策[326,328],支持其理解疾病和建议的治疗[337]。

8.2.2 多学科心房颤动团队

来自于由专家到全科医生,和由医师到合作的健康从业人员组成的工作代表是综合管理模式的基本架

构。多学科 AF 团队的方法包括有效的人际交往和交流技巧、教育和 AF 管理的专门知识,也包括使用专

门的技术。这一方法强调重新设计日常实践的重要性,从某种角度鼓励非专业人员和合作的健康从业人员

在患者教育和协同照护中的重要作用,而专家负有医疗责任。文化和宗教差异将决定 AF 团队的构成。

8.2.3 非专业人员的作用

一些非专业的健康照护人员,如初级保健医师具有丰富的卒中预防和 AF 患者初步管理的专门知识。

其他人可能需要进行这方面知识的培训。AF 管理的其他方面(如评价合并的心血管疾病、抗心律失常药

物治疗或介入治疗)通常需要专家介入。综合的 AF 管理结构应当支持由适当地方的非专业人员进行初始

治疗,提供专业知识的准备,以优化 AF 管理。

8.2.4 用于支持心房颤动照护的技术

技术,如决策支持软件,当用于加强专家建议时,具有潜在的加强实施循证管理、改善转归的作用[338]。电子工具能够保证在 AF 团队内部的协调沟通。为了支持更广泛地使用这种技术,工作组以免费的智

能手机 APP 的形式,为 AF 健康管理人员和 AF 患者提供数字化决策工具。

对综合管理方法的推荐

推荐 推荐

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文献

对所有 AF 患者均应当考虑采用结构化的护理和随访结合的综合方

法,旨在改善指南的依从性,减少住院和死亡率。

Ⅱa B 330-

332

为了个体化管理患者的意愿和提高长期治疗的依从性,应当考虑将

患者放在决策的中心位置。

Ⅱa C 330,332

,334

AF:心房颤动;

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8.3 心房颤动患者的诊断性检查

AF 患者经常同时伴有未被诊断的其他心血管疾病。因此,所有 AF 患者都将从全面心血管评估中获益[339]。

8.3.1 对所有心房颤动患者推荐的评估措施

应当采集完整的医疗史,所有患者均应接受临床评估,包括全面评估合并的疾病、确定 AF 的类型、

评估卒中风险和 AF 相关症状,以及评估心律失常相关并发症如血栓栓塞或 LV 功能减退。推荐做 12 导联

ECG 确定疑似 AF 的诊断,检测 AF 的心室率,筛查传导系统病变、心肌缺血以及结构性心脏病的表现。

首次血液检查应当评估甲状腺和肾功能,以及血清电解质和全血常规。推荐对所有 AF 患者做经胸超声心

动图以指导治疗决策。经胸超声心动图应当用于识别结构性心脏病(如瓣膜疾病)、评估 LV 大小和功能

(收缩和舒张)、心房大小以及右心功能[339,340]。尽管生物标记物如钠尿肽在 AF 患者中增高,但没有充分

的数据表明血液参数是 AF 的独立标志物[341-343]。

8.3.2 在特定心房颤动患者中的额外检查

在 AF 患者中动态 ECG 监测能够评估室率控制是否充分、与 AF 复发相关的症状以及检出阵发性 AF

的局灶诱发因素。经食道超声心动图(TOE)可用于进一步评估瓣膜性心脏病以及除外心脏血栓,尤其是

LAA 的血栓,以便于早期复律或导管消融[344]。有心肌缺血症状或体征的患者视情况而定,应当接受冠状

动脉造影或负荷试验。对于存在脑缺血或卒中征象的 AF 患者,推荐进行脑部计算机体层成像(CT)或磁

共振成像(MRI),以检出卒中和支持相关急诊和长期抗凝治疗的决策。左心房钆对比剂 MRI 延迟增强显

像[345-347],心脏 MRI 的 T1 像[347],以及心腔内超声[348]可能有助于指导 AF 的治疗决策,但是需要在多中心

研究中进一步证实。

8.4 结构化的随访

大多数 AF 患者需要规律随访,以保证持续的优化治疗。随访可能在初级医疗保健机构中进行,由经

训练的专业护士、心血管医师或 AF 专科医师进行[325,330]。专科医师应当协调管理和随访。随访应当确保管

理计划的实施,持续的随诊患者以及必要时调整治疗。

心房颤动患者诊断检查的推荐

推荐 推荐

类别

证据

水平

参考

文献

需要 ECG 记录确定 AF 的诊断 Ⅰ B 349

推荐对所有 AF 患者进行充分的心血管评估,包括确切的病史、仔

细的临床检查和合并疾病的评估。 Ⅰ C

推荐对所有 AF 患者进行经胸超声心动图检查,以指导治疗 Ⅰ C 339

对选定的患者应考虑长期 ECG 监测,以评估有症状的患者室率控制

是否充分,以及症状是否与 AF 发作相关 Ⅱa C

AF:心房颤动;ECG:心电图

8.5 心房颤动管理目标的确定

AF 管理包括影响预后(抗凝和心血管疾病的治疗)的治疗和主要提供症状获益的治疗(室率控制和

节律控制,表 10)。当患者不能直接感受到获益时,需要向患者仔细解释治疗的预后获益。如果症状能够

控制,即使 AF 复发,节律控制治疗也是成功的。在管理开始时,向每个患者解释预期获益可防止不合理

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的期望,有可能优化生活质量。

9.心房颤动患者中的卒中预防治疗

OAC 治疗能够预防大多数 AF 患者的缺血性卒中,并能延长生命[38,39,42,194,201,329,350-352]。在卒中风险水

平不同的患者中,OAC 治疗均优于不治疗或阿司匹林治疗的[353,354]。净临床获益几乎普遍存在,除非患者

卒中风险非常低,因此,OAC 应当用于绝大多数 AF 患者(图 8)。尽管有这些证据,OAC 治疗不足或提

前终止仍然常见。抗凝治疗的出血事件包括严重和令人厌烦的出血,即可预期的“高出血风险”、需要监

测和需要调整 VKA 剂量,是最常见的撤药或停止 OAC 治疗的原因[352,355-359]。然而,不用 OAC 时的卒中

风险相当大,通常超过 OAC 的出血风险,即使是在老年、有认知功能障碍的患者或频繁跌倒或虚弱的患

者中也是如此[360,361]。阿司匹林的出血风险与 VKA[362]或 NOAC[354,363]治疗的出血风险没有差别,且正是

VKA 和 NOACs,而不是阿司匹林,能够有效预防 AF 患者的卒中[38,354,362,363]。

9.1 卒中和出血风险的预测

9.1.1 卒中和系统性栓塞的临床风险评分

临床简单实用的 AF 患者中卒中风险分层标准,是 20 世纪 90 年代末期根据一些小型队列研究开发出

来的,后来,在较大的人群中进行了校正并得以验证[364-368]。CHA2DS2-VASc 评分的引入(表 11)简化了

AF 患者中 OAC 治疗的初始决策。自从 2010 年首次编入 ESC 指南以来[369],它已被广泛应用[370]。我们推

荐在 AF 患者中以 CHA2DS2-VASc 评分评估卒中风险[368]。通常来说,没有临床卒中危险因素的患者不需

要抗栓治疗,而有卒中危险因素(即 CHA2DS2-VASc 评分≥1 分的男性以及≥2 分的女性)的患者可能从

OAC 中获益。

此外,不是很确定的卒中危险因素包括 VKA 治疗患者中国际标准化比值(INR)不稳定和治疗范围内

时间(TTR)低、既往的出血或贫血、酗酒和其他降低治疗依从性的标志、CKD、高敏肌钙蛋白增高以及

N-末端 B 型脑钠肽前体增高。

9.1.2 在 CHA2DS2-VASc 评分 1 分的男性和 2 分的女性患者中的抗凝治疗

已在卒中高危患者中进行了许多项研究 OAC 治疗 AF 患者的对照试验 [38,39,42,194,201,329,351,352]。因此,

强有力的证据表明,CHA2DS2-VASc 评分≥2 分的男性和 CHA2DS2-VASc 评分≥3 分的女性,可从 OAC 治

疗获益。幸运的是,在有一项临床危险因素的患者(如 CHA2DS2-VASc 评分 1 分的男性和 2 分的女性)

中,我们现在有越来越多的关于卒中风险的证据基础,尽管这在很大程度上依赖于在没有服用 OAC 的患

者中观察到的卒中发生率。在许多这样的患者中,抗凝治疗似乎能够带来临床获益[371-375]。由于转归、人

群和抗凝状态不同,卒中率和血栓栓塞率在 CHA2DS2-VASc 评分 1 分和 2 分的患者中有很大不同(在线

表 1)[371,376,377,1041]。因此,我们对具有指南中提出的一项额外卒中危险因素的男性和女性的卒中风险进行

了分析(在线表 1,最后一行)。对于评分为 1 分的男性和 2 分的女性,在权衡了预期的卒中风险降低、

出血风险和患者的意愿后,应当考虑用 OAC。重要的是,年龄(65 岁及以上)可带来较高且持续增加的

卒中风险,同时也使其他因素(如心力衰竭和性别)风险增高。因此,在只有一项 CHA2DS2-VASc 危险因

素的患者中进行抗凝决策时,应当考虑个体化的风险权衡以及患者的意愿,除非是女性。在没有其他卒中

危险因素时,女性似乎不增高卒中风险(在线表 1)[378,379]。

在选定的患者中,测定肌钙蛋白(高敏肌钙蛋白 T 或 I)和 N-末端 B 型脑钠肽前体可能提供额外的预

后信息[380-382]。在将来,基于生物学标记物的风险评分,可能有助于更好地对患者进行分层(如那些真正

卒中低风险的患者)[75,382]。

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表 10 基于目标的随访

类别 干预 随访项目 绩效指标

预后 控制合并疾病(给

出相关例子)

肥胖

高血压

心力衰竭

冠状动脉疾病

糖尿病

瓣膜性心脏病

体重下降

血压控制

心力衰竭治疗和住院

他汀和抗血小板治疗

血运重建

血糖控制

瓣膜修复或置换

预后 抗凝治疗 适应证(风险水平;时机如心

脏复律后)。

依从性(NOAC 或 VKA)和

INR(如用 VKA)。

NOAC 剂量(合并用药,年龄,

体重,肾功能)。

卒中

出血

死亡

主要症状

部分预后

室率控制 症状

平均静息心率<110bpm

改良的 EHRA 评分

心力衰竭状态

LV 功能

运动能力

入院

治疗并发症

目前症状 节律控制 症状 vs.副作用

排除促心律失常作用(PR,

QRS,QTc 间期)

治疗实施和

依从性关联

患者教育和自我管

理能力

知识(关于疾病;关于治疗;

关于管理目标)

能力(如果……需要做什么)

治疗依从性

定向教育,最好基于系统

性清单

长期照护管

理相关

照护者参与 谁?(配偶;GP;家庭护士;

药师)

清楚说出参与作用

知识和能力

任务绩效的定向评估

(如通过患者卡片)

分发药物

随访记录

b.p.m:次/分;mEHRA symptoms scale:改良的欧洲心律协会症状标准;GP:全科医生;INR:国

际标准化比值;LV:左心室;NOAC:非维生素 K 拮抗剂类口服抗凝药;VKA:维生素 K 拮抗

剂。

9.1.3 出血的临床风险评分

已开发了几个出血风险评分,主要是在应用 VKA 的患者中。这些包括 HAS-BLED[高血压、肾功能/

肝功能异常(各 1 分)、卒中、出血病史或出血倾向、INR 不稳定、老年(>65 岁)、合用药物/酒精

(各 1 分)],ORBIT(更好的治疗心房颤动的结局注册研究) 以及晚近的 ABC(年龄、生物标记物、临

床病史)出血评分,也利用了特定的生物标记物[383-385]。卒中和出血风险因子是重叠的(表 11 和 12 进行

了比较)。例如,在 AF 患者中,老年既是缺血性卒中也是出血的重要预测因子之一[386,387]。一次高出血风

险评分通常并不引起 OAC 撤药。但是,应当识别出血风险因子,对可治疗的因素予以纠正(见 8.5 节)。

表 12 详细提供了可改变的出血风险因子。

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卒中和出血风险预测的推荐

推荐 推荐

类别

证据

水平

参考

文献

推荐用 CHA2DS2-VASc 评分预测 AF 患者的卒中风险。

Ⅰ A

368,371,

386

对于口服抗凝剂的 AF 患者,应当考虑出血风险评分,以识别可改

变的主要出血危险因素。 Ⅱa B

384,386,

387,389-

392

可考虑用生物标记物如高敏肌钙蛋白和钠尿肽进一步细分 AF 患者

的卒中和出血风险。 Ⅱb B 339

AF:心房颤动;CHA2DS2-VASc: 充血性心力衰竭,高血压,年龄≥75 岁(2 分),糖尿病,卒中(2 分),血管

疾病,年龄 65-74 岁,性别(女性);OAC:口服抗凝剂

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9.2 卒中预防

9.2.1 维生素 K 拮抗剂

华法林和其他 VKAs 是首先被用于 AF 患者的抗凝剂。与对照组相比(阿司匹林或不治疗),VKA 治

疗降低 2/3 的卒中风险和 1/4 的死亡[38]。在世界范围内 VKAs 已用于很多患者,取得了良好效果[394-396],这

在 NOAC 试验中的华法林组得到了反映(见 9.2.2 节)。VKAs 的使用受到其治疗区间窄,必须频繁监测

和调整剂量的限制,但是当 VKAs 治疗达到足够的治疗范围内时间(TTR)时,在 AF 患者中能够有效地

预防卒中。临床参数有助于识别在 VKA 治疗中有可能达到适宜的 TTR 的患者[397]。这些在 SAMe-TT2R2

评分中进行了总结。这方面得分好的患者,予以 VKA 治疗时,与得分不好的患者相比有较高的平均

TTR[398,399]。对于合并风湿性二尖瓣疾病和/或植入机械瓣的 AF 患者,目前 VKAs 是唯一安全的治疗[400]。

9.2.2 非维生素 K 拮抗剂类口服抗凝剂

在 AF 卒中预防中,NOACs,包括直接凝血酶抑制剂达比加群和Ⅹa 因子抑制剂阿哌沙班、依度沙班

和利伐沙班,是 VKA 合适的替代品(表 13)。这些药物在临床实践中的使用迅速增加[401]。所有的

NOACs 效果均可预测(起效和失效),不需要规律的抗凝监测。Ⅲ期临床试验已经对 NOACs 的剂量进行

了仔细的选择,包括应在临床实践中遵循的应减少剂量的明确规则(表 13)。

表 11 CHA2DS2-VASc 评分系统中,卒中、短暂性脑缺血发作以及系统栓塞的临床危险因素

CHA2DS2-VASc 危险因素 分数

充血性心力衰竭

心力衰竭的症状/体征或左室射血分数降低的客观证据

+1

高血压

至少两次静息血压>140/90mmHg 或正在降压治疗

+1

年龄≥75 岁 +2

糖尿病

空腹血糖>125mg/dL(7mmol/L)或口服降糖药物和/或胰岛素治疗

+1

既往卒中,短暂性脑缺血发作,或血栓栓塞 +2

血管疾病

既往心肌梗死,外周动脉疾病,或主动脉斑块

+1

年龄 65-74 岁 +1

性别(女性) +1

CHA2DS2-VASc: 充血性心力衰竭,高血压,年龄≥75 岁(2 分),糖尿病,卒中(2 分),血管

疾病,年龄 65-74 岁,性别(女性)

9.2.2.1 阿哌沙班

在 ARISTOTLE(阿哌沙班降低心房颤动卒中和其他血栓栓塞事件的研究)试验中[319],与华法林相

比,阿哌沙班 5mg,每日两次,降低卒中或系统性栓塞 21%,同时主要出血事件减少 31%,全因死亡减少

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11%(均有统计学显著意义)。阿哌沙班出血性卒中和颅内出血率较低,但不包括缺血性卒中。胃肠道出

血率在两个治疗组相似[402]。

在 AF 患者中,阿哌沙班是唯一与阿司匹林作过比较的 NOAC;与阿司匹林相比,阿哌沙班明显降低

卒中或系统性栓塞 55%,大出血或颅内出血率没有或仅有很小差异[354,403]。

9.2.2.2 达比加群

在 RE-LY(长期抗凝治疗的随机化评估)研究中[318,404],与华法林相比,达比加群 150mg,每日两

次,减少卒中和系统性栓塞 35%,而大出血事件没有明显差异。达比加群 110mg,每日两次,对预防卒中

和系统性栓塞不劣于华法林,大出血事件降低了 20%。两种剂量的达比加群均明显降低出血性卒中和颅内

出血。达比加群 150mg,每日两次,明显降低缺血性卒中 24%和血管死亡率 12%,但胃肠道出血明显增加

50%。在两种剂量的达比加群间,心肌梗死发生率没有明显差异[318,404],这一结果在大型授权后分析中未

能重复 [396]。这些观察性数据也重复了 RE-LY 试验中,主要是在使用高剂量(150mg,每日两次)达比加

群治疗的患者中,达比加群获益优于 VKA[396]。

9.2.2.3 依度沙班

在 ENGAGE AF-TIMI48(使用新一代 Xa 有效抗凝治疗心房颤动——心肌梗死溶栓治疗 48)试验中[321],依度沙班 60mg 一日一次和依度沙班 30mg 一日一次(对某些患者用更小剂量,表 13)与剂量调整的

华法林进行了比较[405]。依度沙班 60mg 每日一次不劣于华法林(表 13)。在一项治疗分析中,与华法林

相比,依度沙班 60mg 一日一次明显降低卒中或系统性栓塞 21%,明显降低大出血事件 20%,而依度沙班

30mg 一日一次在预防卒中和系统性栓塞方面不劣于华法林,但是明显降低大出血事件 53%。与华法林相

比,随机分配至依度沙班 60mg 一日一次或依度沙班 30mg 一日一次的患者,心血管死亡率均降低。仅仅

大剂量方案得到批准用于 AF 卒中预防

9.2.2.4 利伐沙班

在 ROCKET-AF(心房颤动中比较每日一次口服直接 Xa 因子抑制剂利伐沙班与维生素 K 拮抗剂预防

卒中和栓塞的试验)中[320],患者被随机分为利伐沙班 20mg 每日一次或 VKA 组,对根据 Cockroft–Gault

公式估测 CrCl 为 30-49mL/min 的患者剂量调整至 15mg/日(表 13)。在意向性治疗分析中,利伐沙班在

预防卒中和系统性栓塞方面不劣于华法林,而按实际治疗分析时与华法林相比,卒中或系统性栓塞减少

21%,达到统计学优势。与 VKA 相比,利伐沙班不降低死亡率、缺血性卒中或大出血事件率。与华法林

相比,利伐沙班使胃肠道出血事件增多,但出血性卒中和颅内出血明显减少。在作为批准后管理过程一部

分的授权后分析中,报道事件率相当[406,407]。

9.2.3 非维生素 K 拮抗剂类口服抗凝剂还是维生素 K 拮抗剂

VKAs 和 NOACs 对预防 AF 患者的卒中均有效。一项对华法林与 NOACs 比较的关键研究中高剂量治

疗组的荟萃分析[39],包括 42411 名接受一种 NOAC 和 29272 名接受华法林的患者。在这些剂量上,与华法

林相比,NOACs 明显减少卒中或系统性栓塞事件 19%(RR 0.81; 95% CI 0.73–0.91;P=0.0001),主要

由出血性卒中减少所致(RR 0.49; 95% CI 0.38–0.64;P=0.0001)。随机化接受 NOAC 治疗的患者死亡

率低 10%(RR 0.90;95% CI 0.85 – 0.95; P= 0.0003),颅内出血减少一半(RR 0.49; 95% CI 0.38–

0.64;P= 0.0001),但胃肠道出血事件更多(RR 1.25;95% CI 1.01 – 1.55; P=0.04)[39]。NOAC 相关的

卒中减少在所有亚组中一致,而在 INR 控制不佳的中心,NOACs 出血相对减少更多(交互作用

P=0.022)。值得注意的是,与华法林相比,NOACs 组颅内出血实质性的降低似乎与 INR 控制质量不相关[408,409]。

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ESC Guidelines

表 12 基于出血风险评分,抗凝治疗的患者中可纠正和不可纠正的出血危险因素

高血压(尤其是收缩压>160mmHg)a,b,c

在口服维生素 K 拮抗剂的患者中,INR 波动大或治疗范围内时间<60%a

可诱发出血的药物,如抗血小板药物和非甾体类抗炎药 a,d

酒精过量(≥8 份/周)a,b

贫血 b,c,d

肾功能受损 a,b,c,d

肝功能受损 a,b

血小板数量或功能降低 b

年龄 e(>65 岁)a(≥75 岁)b,c,d

大出血病史 a,b,c,d

既往卒中 a,b

依赖于透析的肾病或肾移植 a,c

肝硬化 a

恶性肿瘤 b

遗传因素 b

生物标记物为基础的出血风险因子

高敏肌钙蛋白 e

生长分化因子 15e

血清肌酐/估测的 CrCle

ABC:年龄,生物标记物,临床病史;ATRIA:心房颤动中的抗凝和危险因素;

CKD:慢性肾病;CrCl:肌酐清除率;HAS-BLED:高血压,肝功/肾功异常(每项 1 分),卒中,出血史或倾向,

INR 波动大,老年(>65 岁),合并使用药物/酒精(每项 1 分);HEMORR2HAGES:肝病或肾病,酒精滥用,恶

性肿瘤,老年(年龄>75 岁),血小板数量或功能下降,再次出血风险(以前出血,2 分),高血压(未控制),

贫血,遗传因素(CYP2C9 多态性),额外的跌倒风险(包括神经精神性疾病),卒中;INR:国际标准化比值;

ORBIT:更好的知情治疗心房颤动的结局注册研究;TTR:治疗范围内时间;VKA:维生素 K 拮抗剂

a:来自于 HAS-BLED 评分 384

b:来自于 HEMORR2HAGES 评分 383

c:来自于 ARTIA 评分 385

d:来自于 ORBIT 评分 388

e:ABC 出血评分 387

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表 13 已获批准的非维生素 K 拮抗剂类口服抗凝剂特点比较

达比加群(RE-

LY)

利伐沙班(ROCKET-AF) 阿哌沙班

(ARISTOTLE)

依度沙班(ENGAGE AF-

TIMI48)

机制 口服直接凝血酶抑制剂 口服直接Ⅹa 因子抑制剂 口服直接Ⅹa 因子抑制剂 口服直接Ⅹa 因子抑制剂

生物利用

度%

6 空腹 66,进食 80-100 50 62

达峰时间,

小时

3 2-4 3 1-2 半衰期,小

12-17 5-13 9-14 10-14 清除 80%经肾脏 66%经肝脏,33%经肾脏 27%经肾脏 50%经肾脏 剂量 150mg 每日两次或 110mg 每日

两次

20mg,每日一次 5mg 每日两次 60mg 每日一次或 30mg 每日一次

在选定的患

者中减少剂

如果 CrCl 30-49mL/min,利伐沙班 15mg 每日一次 如有以下至少 2 项:年龄≥80

岁,体重≤60kg 或血清肌酐≥

1.5mg/dL(133μmol/L),则

阿哌沙班 2.5mg 每日两次

如果有以下任何一项:肌酐清除率 30-

50mL/min,体重≤60kg,合并使用维拉帕米或奎

尼丁或决奈达隆,则依度沙班 60mg 减少至 30mg

每日一次,依度沙班 30mg 减少至 15mg 每日一

研究设计 随机化,开放标签 随机化,双盲 随机化,双盲 随机化,双盲 患者数量 18113 14264 18201 21105 随访时间,

2 1.9 1.8 2.8 随机化分组 剂量调整的华法林 vs.盲法剂量

的达比加群(150mg 每日两次

或 110mg 每日两次)

剂量调整的华法林 vs.利伐沙班 20mg,每日一次 剂量调整的华法林 vs.阿哌沙

班 5mg,每日两次

剂量调整的华法林 vs.盲法剂量的达比加群

(60mg 每日一次或 30mg 每日一次)

年龄,岁 71.5 ± 8.7 (mean ± SD) 73 (65–78)[中位数(四分位范围)] 70 (63–76) [中位数(四分位范

围)]

72(64-78)[中位数(四分位范围)] 男性,% 63.6 60.3 64.5 61.9 CHADS2评

分(平均)

2.1 3.5 2.1 2.8

华法林 达比加群 150 达比加群 110 华法林 利伐沙班 华法林 阿哌沙班 华法

依度沙班 60 依度沙班 30

n=6022 n=6076 n=6015 n=7133 n=7131 n=9081 n=9120 n =

7036

n = 7035 n = 7034

事件

率%/年

事件率%/年

(RRvs.华法林)

事件率%/年

(RRvs.华法

林)

事件

率%/

事件率%/年

(HRvs.华法林)

事件

率%/年

事件率%/年

(HRvs.华法

林)

事件

率%/

事件率%/年

(HRvs.华法

林)

事件率%/年

(HRvs.华法林)

卒中/系统

性栓塞

1.72 1.12 (0.65,0.52–

0.81;非劣效 P

和优势 P 值

<0.001)

1.54 (0.89,

0.73–1.09;

非劣效 P <0.001)

2.4 2.1 (0.88, 0.75–1.03;

非劣效 P

<0.001, 优势 P=

0.12)

1.60 1.27 (0.79, 0.66–

0.95;

非劣效 P

<0.001 ;,

优势 P = 0.01

1.80 1.57 (0.87,

0.73–1.04;

非劣效 P

<0.001 优势

P= 0.08

2.04 (1.13, 0.96–

1.34;

非劣效 P = 0.005

优势 P = 0.10

缺血性卒中 1.22 0.93 (0.76,

0.59–0.97;

P = 0.03)

1.34 (1.10,0.88–

1.37;P = 0.42)

1.42 1.34 (0.94; 0.75–

1.17;P = 0.581)

1.05 0.97 (0.92, 0.74–

1.13; P = 0.42)

1.25 1.25 (1.00, P =

0.97) 0.83–

1.19;

1.77 (1.41, 1.19–

1.67; P <0.001

出血性卒中 0.38 0.10 (0.26,

0.14–0.49;P

<0.001)

0.12 (0.31,

0.17–0.56;P

<0.001)

0.44 0.26 (0.59; 0.37–

0.93;

P = 0.024)

0.47 0.24 (0.51, 0.35–

0.75; P <0.001)

0.47 0.26 (0.54,

0.38–0.77; P

<0.001)

0.16 (0.33, 0.22–

0.50; P <0.001)

大出血 3.61

3.40 (0.94,0.82–

1.08;P = 0.41)

2.92 (0.80,0.70–

0.93;P = 0.003)

3.45 3.60 (1.04; 0.90-

2.30;P = 0.58)

3.09 2.13 (0.69, 0.60–

0.80;

P <0.001)

3.43 2.75 (0.80,

0.71–0.91; P

<0.001)

1.61 (0.47, 0.41–

0.55; P <0.001)

颅内出血 0.77

0.32 (0.42,0.29–

0.61;P <0.001)

0.23 (0.290.19–

0.45;P <0.001)

0.74 0.49 (0.67; 0.47–

0.93;

P = 0.02)

0.80 0.33 (0.42, 0.30–

0.58; P <0.001)

0.85 0.39 (0.47,

0.34–0.63; P

<0.001)

0.26 (0.30, 0.21–

0.43; P <0.001)

胃肠道大出

1.09

1.60 (1.48,1.19–

1.86;P <0.001)

1.13 (1.04,

0.82–1.33;

P = 0.74)

1.24 2.00 (1.61; 1.30-

1.99;

P < 0.001)

0.86 0.76 (0.89, 0.70–

1.15; P = 0.37)

1.23 1.51 (1.23,

1.02–1.50; P =

0.03)

0.82 (0.67, 0.53–

0.83; P <0.001)

心肌梗死 0.64

0.81 (1.27,0.94-

1.71;P = 0.12)

0.82 (1.29, 0.96-

1.75;P = 0.09)

1.12 0.91 (0.81; 0.63–

1.06;

P = 0.12)

0.61 0.53 (0.88, 0.66–

1.17; P = 0.37)

0.75 0.70 (0.94,

0.74–1.19; P =

0.60)

0.89 (1.19, 0.95–

1.49; P = 0.13)

任何原因死

4.13

3.64 (0.88,0.77–

1.00;P = 0.051)

3.75(0.91,

0.80–1.03;

P = 0.13)

2.21 1.87 (0.85; 0.70–

1.02;

P = 0.07)

3.94 3.52 (0.89, 0.80–

0.99; P = 0.047)

4.35 3.99 (0.92,

0.83–1.01; P =

0.08)

3.80 (0.87, 0.79–

0.96; P = 0.006)

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ESC GUIDELINES

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9.2.4 合并慢性肾病的心房颤动患者中的口服抗凝治疗

在大数据环境中,CKD 与卒中和出血相关[410,411]。抗凝治疗能够安全用于 AF 伴有中度或中到重度 CKD

(肾小球滤过率(GFR)≥15mL/min)的患者:SPAF(心房颤动的卒中预防)Ⅲ试验,对伴有 3 期 CKD

(估测 GFR<59mL/min/1.73m2)的 805/1936 名参与者进行了随机,报告用华法林治疗(INR2-3)效果良

好[412]。这一发现受到大型瑞典数据库的支持:其中在以华法林治疗的 CKD 合并 AF 的患者中卒中风险降

低(调整的 HR 0.76; 95% CI 0.72–0.80)[413],而出血也有轻度增高,尤其是在治疗起始时[414]。在一篇对主

要 NOAC 试验的荟萃分析中,轻度或中度 CKD 的患者接受 NOACs 治疗,其卒中、系统性栓塞或主要出

血事件率低于华法林[415]。对于服用 NOAC 的 AF 患者,应当定期监测肾功能,以便进行剂量调整(表

14),并细化风险评估[416]。

表 14 根据 PHASE Ⅲ试验评估调整 NOACs 剂量(根据 Hart 等[316]修改)

达比加群

(RE-LY)318,425

利伐沙班

(ROCKET-AF)320,426

阿哌沙班

(ARISTOTLE)319,427

依度沙班

(ENGAGE AF-

TIMI 48)321

肾脏清除率 80% 35% 25% 50%

患者数量 18113 14264 18201 21105

剂量

150mg 或 110mg

每日两次 20mg,每日一次 5mg,每日两次

60mg(或 30mg)

每日一次

CKD 排除标

准 CrCl<30ml/min CrCl<30ml/min

血清肌酐>2.5mg/dL 或

CrCl<25ml/min CrCl<30ml/min

CKD 剂量调

整 无

如果 CrCl <30-

49ml/min,则

15mg,每日一次

如果血清肌酐≥1.5mg/dL

(133μmol/L),以及年

龄≥80 岁或体重≤60kg,

则 2.5mg,每日两次

如果 CrCl<

50ml/min,则 30mg

(或 15mg)每日一

CKD 患者比

20% CrCl 30-

49ml/min

21% CrCl 30-

49ml/min 15% CrCl 30-50ml/min

19% CrCl <

50ml/min

卒中和系统

性栓塞减少

与 CKD 无交互作

用 与 CKD 无交互作用 与 CKD 无交互作用 NA

与华法林相

比主要出血

减少

两个剂量组,

eGFR>80 ml/min

的患者中,达比加

群主要出血减少更

主要出血相似 阿哌沙班主要出血减少 NA

CKD:慢性肾病;CrCl:肌酐清除率;GFR:肾小球滤过率;NA:未提供

9.2.5 透析的心房颤动患者的口服抗凝治疗

大约 1/8 的透析患者合并 AF,发生率为 2.7/100 人·年[417]。AF 与透析患者死亡率增加相关[417]。没有

随机化研究评估血液透析患者中的 OAC[418],在严重 CKD 患者(CrCl<25-30mL/min)中没有 NOACs 的

对照试验[318-321]。在透析患者数据库的分析中,华法林使用对卒中风险为中性或与增加卒中风险相关[419-

421],其中包括加拿大人群为基础的分析(调整的卒中 HR 1.14; 95% CI 0.78–1.67;调整的出血 HR 1.44;

95% CI 1.13–1.85)[422]。相反,来自于丹麦的数据表明,在肾脏替代治疗的患者中,OAC 治疗可获益[423]。因此,尚需在透析 AF 患者中进行抗凝治疗(VKA 和 NOACs)的对照研究[424]。

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9.2.6 需要进行肾脏移植的心房颤动患者

没有评估肾脏移植后患者中 OAC 的随机化研究。在移植肾脏患者中应当根据 eGFR 指导 NOAC 治疗

处方。应当考虑可能存在的 OAC 与免疫抑制剂的药代动力学的相互作用。

9.2.7 抗血小板治疗能否作为口服抗凝剂的替代

支持单独抗血小板药物治疗 AF 预防卒中的证据十分有限[38,428-430]。VKA 治疗预防卒中、系统性栓

塞、心肌梗死和血管性死亡,优于阿司匹林和氯吡格雷单用或双联抗血小板治疗(用华法林年风险率为

3.9%,而用阿司匹林和氯吡格雷年风险率为 5.6%)[431]。在高 TTR 的 VKA 治疗的患者中甚至获益更大[432]。抗血小板治疗增加出血风险,尤其是双联抗血小板治疗(单药抗血小板治疗 2.0% vs. 1.3%,P<

0.001)[433],出血率与 OAC 相似[354,362,431,434]。因此,不推荐抗血小板治疗用于 AF 患者的卒中预防。

9.3 左心耳封堵和切除

9.3.1 左心耳封堵器械

介入性 LAA 封堵[446-449],以及经验有限的经皮 LAA 结扎,主要见于观察性研究和注册研究的报告。

仅仅一种器械(Watchman○R)与 VKA 在随机化试验中[PROTECT AF(在心房颤动患者中 Watchman 左心

耳封堵系统预防血栓的试验),见网页表 2,和 PREVAIL(心房颤动患者中 Watchman 左心耳封堵器与长

期华法林治疗的前瞻性随机化评估试验)]进行了比较[449-451]。这些数据中,中等卒中风险的 AF 患者,对

预防卒中 LAA 封堵器不劣于华法林治疗,并且在继续随访的患者中可能有较低的出血率[452,453]。在对这两

项试验及其相关注册研究的患者水平的荟萃分析中证实了这些数据[453]。LAA 封堵器在有 OAC 禁忌证的患

者中也减少卒中风险[454,455]。植入过程可引起严重并发症[446,456-458],一篇来自于保险数据库和系统评价的

分析,报道了较高的事件率,可能存在一定程度的报告偏倚[446,456]。最近,一项大型欧洲注册研究报告了

高的植入成功率(98%),30 天时 可接受的操作相关并发症率为 4%[459]。大多数曾经考虑不适合 OAC 的

患者,看来对当今管理的 OAC 表现得相当好[396,407,460]。迫切需要进行有充分把握度的对照研究,以明确这

些器械的最佳使用,包括在确实不适合 OAC 或在 OAC 治疗期间卒中的患者中,LAA 封堵器的使用,随

机化比较 LAA 封堵器与 NOAC,以及评估在 LAA 治疗后可接受的最小抗血小板治疗方案。

9.3.2 外科左心耳封堵或切除

几十年来已经使用不同技术在心脏手术同时进行外科 LAA 封堵或切除。多项观察性研究表明了外科

LAA 封堵/切除的可行性和安全性,但是仅有有限的对照试验的数据可用[461-464]。残余 LAA 血流或不完全

LAA 切除可增加卒中风险[465]。在大多数研究中,LAA 封堵/切除是在其他心内直视手术中进行的,晚近更

多是联合 AF 外科消融[463]或作为独立的胸腔镜手术。2015 年报告了一项评估同时进行 AF 外科治疗和

LAA 封堵作用的随机化试验,在接受 AF 外科治疗的亚组中,LAA 切除对卒中预防没有明确获益[466]。最

近正在进行一项大型随机化试验[467]。

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ESC Guidelines

心房颤动患者中卒中预防的推荐

推荐 推荐

类别

证据

水平

参考

文献

推荐所有 CHA2DS2-VASc 评分≥2 分的男性 AF 患者口

服抗凝剂治疗用于预防血栓栓塞。 Ⅰ A

38,318–

321,354,

404

推荐所有 CHA2DS2-VASc 评分≥3 分的女性 AF 患者口

服抗凝剂治疗用于预防血栓栓塞。 Ⅰ A 38,318–321,

354, 404

在 CHA2DS2-VASc 评分 1 分的男性 AF 患者,考虑到个

体特征和患者意愿,应当考虑口服抗凝剂治疗用于预防

血栓栓塞。

Ⅱa B 371,375-377

在 CHA2DS2-VASc 评分 2 分的女性 AF 患者,考虑到个

体特征和患者意愿,应当考虑口服抗凝剂治疗用于预防

血栓栓塞。

Ⅱa B 371, 376,

377

推荐维生素 K 拮抗剂治疗(INR2.0-3.0 或更高)用于中

到重度二尖瓣狭窄或机械心脏瓣膜的 AF 患者的卒中预

防。

Ⅰ B 274,435-440

当 AF 患者开始口服抗凝剂治疗时,如果其适于应用

NOAC(阿哌沙班,达比加群,依度沙班,或利伐沙班),

推荐 NOAC,优于维生素 K 拮抗剂。

Ⅰ A 39,318–321,

404

当患者使用维生素 K 拮抗剂治疗时,治疗范围内时间

(TTR)应当尽可能保持高水平并严密监测。 Ⅰ A 395, 432,

441-444

已经使用维生素 K 拮抗剂的 AF 患者,如果尽管依从性

良好但 TTR 控制不佳,或患者没有 NOAC 禁忌证(如

人工瓣膜)而患者愿意,可以考虑 NOAC 治疗。

Ⅱb A 39, 318,319,

404,408

联合使用口服抗凝剂和血小板抑制剂增加出血风险,在

没有其他血小板抑制剂适应证的 AF 患者中应当避免。

(有害) B 429, 445

在没有其他卒中危险因素的男性或女性 AF 患者中,不

推荐抗凝或抗血小板治疗用于卒中预防。

(有害) B

368, 371,

376, 377

不管卒中风险程度如何,不推荐抗血小板单药治疗用于

AF 患者卒中预防。

(有害) A 38, 429, 430

不推荐 NOAC(阿哌沙班、达比加群、依度沙班和利伐

沙班)用于机械性心脏瓣膜(证据水平 B)或中到重度

二尖瓣狭窄的患者(证据水平 C)。

(有害) B C

318–321,

400, 404

AF:心房颤动;CHA2DS2-VASc: 充血性心力衰竭,高血压,年龄≥75 岁(2 分),糖尿病,卒

中(2 分),血管疾病,年龄 65-74 岁,性别(女性);INR:国际标准化比值;NOAC:非维生

素 K 拮抗剂类口服抗凝剂;OAC:口服抗凝剂;TTR:治疗范围时间;VKA:维生素 K 拮抗剂

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左心耳封堵或切除的推荐

推荐 推荐

类别

证据

水平

参考

文献

在外科封堵或切除 LAA 后,推荐在有风险的 AF 患者中继续抗凝治

疗以预防卒中。 Ⅰ B 461,462

在有长期抗凝治疗禁忌证(如此前发生无可逆原因的威胁生命的的

出血)的 AF 患者中,可考虑 LAA 封堵用于卒中预防。 Ⅱb B

449,

453,

454

在接受心脏外科手术的 AF 患者中,可考虑外科封堵或切除 LAA 用

于卒中预防。 Ⅱb B 463

在接受胸腔镜 AF 外科手术的患者中,可考虑外科封堵或切除 LAA

用于卒中预防。 Ⅱb B 468

AF:心房颤动;LAA:左心耳

9.4 卒中的二级预防

在 AF 患者中最重要的卒中危险因素是高龄和既往心源性栓塞性卒中或 TIA[382],强调了对这些患者

OAC 治疗的必要性。在第一次卒中或 TIA 后早期,卒中复发风险最高[469,470]。

9.4.1 急性缺血性卒中的治疗

使用重组组织型纤溶酶原激活物(rtPA)全身溶栓,在症状发作 4.5h 内的急性缺血性卒中患者中是有

效且被批准的医疗措施[471]。全身溶栓对 OAC 治疗的患者是禁忌证[472,473]。在 VKA 治疗的患者中如果 INR

低于 1.7[474],或者当使用达比加群的患者活化的部分凝血活酶时间正常、而最后一次服用药物>48h 之前

时,可以使用重组组织型纤溶酶原激活物(基于专家共识)[472]。是否可使用特异性 NOAC 解毒剂[475]然后

再进行全身溶栓仍需研究。在抗凝治疗的患者,如发生颈内动脉远端或大脑中动脉闭塞,在 6h 时间窗内

可进行血栓切除[476]。

9.4.2 短暂性脑缺血发作或缺血性卒中后启动抗凝治疗

缺乏在卒中后的第一天优化使用抗凝剂的数据(肝素、低分子肝素、磺达肝癸钠、VKA、NOAC)。

在急性卒中后 7-14 天,注射用抗凝剂似乎伴有缺血性卒中复发不显著的降低[比数比(OR)0.68; 95% CI

0.44–1.06],但症状性颅内出血明显增加(OR 2.89; 95% CI 1.19–7.01),在最后随访中,死亡或致残率

相似[477]。在大面积卒中的最初几天中,注射用抗凝剂的出血风险似乎超过其卒中预防获益,而 TIA 或小

面积卒中患者可从早期(即刻)起始或继续抗凝治疗中获益。因此,我们建议对于缺血性卒中后 1-12 天之

间的 AF 患者,是否抗凝治疗取决于卒中严重程度(图 9)[478]。我们建议重复脑影像学检查,以确定有转

变为脑出血风险的大面积卒中患者最佳的启动抗凝治疗时机。在卒中存活的 AF 患者中,长期使用 OAC,

包括 VKA[363,479-481]或 NOACs[482]均带来获益。NOACs 治疗转归似乎更好,主要由于颅内出血和出血性卒

中更少(OR 0.44; 95% CI 0.32–0.62)[482]。依度沙班的详细数据尚未发表[321]。如果患者在服用抗凝剂期

间发生卒中或 TIA,应考虑转换为另一种抗凝剂。

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9.4.3 颅内出血后启动抗凝治疗

没有前瞻性研究调查颅内出血后启动 OAC 治疗的获益或风险[483],比较 NOACs 和 VKAs 的随机化试

验均排除了有颅内出血病史的患者。现有证据表明在 4-8 周后可重新启动 AF 患者中的抗凝治疗,尤其是

当出血原因或相关危险因素已得到治疗时(如未控制的高血压,见表 12),这样治疗可减少(缺血性)

卒中复发,降低死亡率[460,484]。如果重新开始抗凝治疗,考虑低出血风险的抗凝剂可能是合理的[49]。图 10

显示了颅内出血后启动或恢复 OAC 的专家共识意见。我们推荐包括卒中医师/神经病学家、心脏病学家、

神经放射学家和神经外科医生在内的多学科决策。

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卒中二级预防的推荐

推荐 推荐

类别

证据

水平

参考

文献

在 AF 患者缺血性卒中后不推荐即刻开始肝素或低分子肝素抗凝

治疗。

(有害)

A 477

患者在抗凝治疗期间发生 TIA 或卒中,是否坚持治疗应当进行评

估和优化。 Ⅱa C

抗凝期间发生中至重度缺血性卒中的患者,在对急性卒中和出血

风险进行多学科评估的基础上,应当中断抗凝治疗 3-12 天。 Ⅱa C

在卒中的 AF 患者中,应当考虑阿司匹林用于卒中二级预防,直到

启动或者重新开始口服抗凝剂。 Ⅱa B 485

如果 INR 超过 1.7(或使用达比加群的患者,如果 aPTT 在正常范

围之外),不推荐用 rtPA 进行全身溶栓。

(有害)

C 472,47

4

有既往卒中的 AF 患者,推荐 NOACs,优于 VKAs 或阿司匹林。 Ⅰ B

363,48

2

在 TIA 或卒中后,不推荐 OAC 和抗血小板药物联合治疗。 Ⅲ

(有害)

B 486

在颅内出血后,如果出血的原因或相关危险因素已得到治疗或控

制,AF 患者可以在 4-8 周后重新启动口服抗凝剂治疗。 Ⅱb B 483,48

34,487

AF:心房颤动;INR:国际标准化比值;NOAC :非维生素 K 拮抗剂类口服抗凝剂;OAC:口服抗凝剂;TIA:短

暂性脑缺血发作;VKA:维生素 K 拮抗剂

9.5 减少抗凝治疗出血的策略

在一篇纳入 47 项研究的荟萃分析中, VKA 相关大出血的总体发生率,在有对照的试验中,为 2.1

(范围 0.9-3.4)/100 人·年,在观察性研究中,为 2.0(范围 0.2-7.6)/100 人·年[488]。尽量减少可治疗的

出血危险因素(见表 12)对减少抗凝剂的出血率看来是最重要的。

9.5.1 未控制的高血压

未控制的高血压增加 OAC 的出血风险[53]。因此,保持收缩压控制良好与抗凝治疗的 AF 患者密切相

关。推荐根据当前的指南治疗确诊的高血压患者[489]。

9.5.2 既往出血事件

出血病史和存在贫血是所有接受 OAC 治疗患者评估的重要部分。出血事件主要是胃肠道。与华法林

相比,达比加群 150mg 一日两次[396,490],利伐沙班 20mg 一日一次[491],以及依度沙班 60mg 一日一次[321]增

加胃肠道出血。胃肠道出血风险在华法林、达比加群 110mg 每日两次[490]以及阿哌沙班 5mg 一日两次[319]之

间相当。最近的观察性分析未能重复这些发现,表明其影响较小[396,492,493]。在已确定出血来源并已纠正的

患者中,可重新开始使用 OAC。对颅内出血的患者,一旦可纠正的出血危险因素(如未控制的高血压)被

纠正后也是如此[460,484]。

9.5.3 波动的国际标准化比值和适当的非维生素 K 拮抗剂类口服抗凝剂剂量

VKA 治疗的 TTR 是大出血的重要预测因子[432,441,494]。因此,我们推荐用 VKA 治疗的患者 INR 目标

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在 2.0-3.0 之间,并保持高水平 TTR(如≥70%[494]),当不能维持高水平 TTR 时,考虑转变为 NOAC 治

疗[444]。NOAC 剂量应当遵循临床试验中减少剂量的评估标准,考虑肾功能、年龄和体重。患者的知情同

意,最好通过综合 AF 管理,似乎是达到这一目标的主要因素。

9.5.4 酗酒

酒精过量是抗凝治疗患者的重要的出血危险因素[384],通过依从性不足、肝病、静脉曲张出血和重大

创伤风险产生影响。在 OAC 治疗的患者中,应当纠正严重酗酒和无节制饮酒的习惯。

9.5.5 跌倒和痴呆

跌倒和痴呆与 AF 患者死亡率增加相关[495],没有证据表明这些情况明显增加颅内出血风险[495,496]。因

此,仅在患者有严重的未控制的跌倒风险(如癫痫或严重多系统萎缩伴有向后跌倒)时不使用抗凝治疗,

或者在经选择的痴呆患者,其看护者不能保证其依从性时不使用抗凝治疗。

9.5.6 基因检测

除了食物和药物交互作用外,多种基因变异影响 VKAs 代谢[497]。已在几项对照临床研究中对有计划

的使用遗传信息来调整 VKA 剂量进行了评估[498-500]。基因检测对华法林的 TTR 或出血风险几乎没有作

用,当前不推荐用于临床[501]。

9.5.7 口服抗凝剂的桥接

大多数心血管介入措施(如经皮冠状动脉介入或起搏器植入)在持续使用 OAC 期间能够安全进行。

当需要中断 OAC 治疗时,桥接似乎不能获益,除非患者有机械性心脏瓣膜:在 1884 名 AF 患者的随机化

研究中,在动脉血栓栓塞结局方面,中断抗凝治疗不劣于肝素桥接治疗(发生率分别为 0.4%和 0.3%),

而大出血风险较低(分别为 1.3%和 3.2%)[502]。为预防卒中,应尽可能减少中断 OAC 治疗。

9.6 抗凝治疗的心房颤动患者出血事件的管理

9.6.1 轻度、中等和严重出血的管理

对发生出血事件的抗凝治疗的 AF 患者的全面评估,应当包括出血部位、起始和出血的严重程度,最

后一次服用 OAC 以及其他抗栓药物的时间,其他影响出血风险的因素如 CKD、酒精滥用及合用的药物。

实验室检查应当包括血红蛋白、红细胞压积、血小板计数、肾功能,以及对服用 VKA 的患者,检查凝血

酶原时间、活化部分凝血活酶时间和 INR。在使用 NOAC 的患者中,除了对服用达比加群的患者可查活化

部分凝血活酶时间外,凝血试验提供不了太多信息。已有很多特异性的凝血试验,包括用于达比加群的稀

释的凝血酶时间(HEMOCLOT) 和用于Ⅹa 因子抑制剂的校准定量抗Ⅹa 因子分析[503]。然而,这些试验

并不总是可及的,且对出血治疗通常不是必需的[504]。

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我们提出一个简单的图表用于管理服用 OAC 患者的出血事件(图 11)。轻微出血事件应当通过支持

性措施如机械压迫或小手术治疗以达到止血目的。在接受 VKAs 的患者中,下一次的 VKA 剂量应当推

迟。NOACs 血浆半衰期短,大约 12h,预计在延迟或停服一次剂量后 12-24h 内停止出血。中度出血事件

的治疗可能需要输血和补液。应当迅速采取直接针对出血病因(如胃镜)的特异性诊断和治疗干预措施。

如果近期(<2-4h)口服 NOAC,服用活性炭和/或洗胃可减少进一步暴露。透析可清除达比加群,但对其

他 NOACs 几乎无效。

对于严重或危及生命的出血事件,需要即刻逆转抗栓作用。对危及生命的出血管理流程制度应有备

案,并随时均可查看,以确保适当的初始管理。对 VKAs,予以新鲜冰冻血浆恢复凝血比维生素 K 更为迅

速,浓缩凝血酶原复合物能够更快地使血液凝固[505]。注册资料表明在使用 VKA 治疗,INR≥1.3 的颅内出

血病例中,联合使用血浆和浓缩凝血酶原复合物死亡率最低[506]。在一项包括了 188 名患者的多中心随机

化试验中,对于接受急诊外科手术或侵入性操作的患者,含有四种因子的浓缩凝血酶原复合物与血浆相

比,能够更快地逆转 INR,并有效止血[507]。在 NOAC 治疗发生严重出血时,如果没有特异性解毒剂,也

可考虑予以浓缩凝血酶原复合物。几种 NOACs 解毒剂正在开发中。Idarucizumab(2015 年已获美国食品

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和药品管理局以及欧洲药品管理局批准)是一种临床上可用的人源化抗体片段,可与达比加群结合,迅速

且呈剂量依赖性地逆转其效果,并且不会过度纠正或产生凝血酶[475]。Andexanet alpha,是经修饰后没有酶

活性的重组人Ⅹa 因子,在健康受试者中给予数分钟后逆转Ⅹa 拮抗剂的抗凝活性,并在输注过程中持续维

持,伴有与临床相关性不确定的凝血活性标记物的一过性增高[508]。另一个正在开发中的药物是

ciraparantag(PER977),一种设计的解毒剂,能够逆转直接凝血酶抑制剂和Ⅹa 因子抑制剂的效果,且能

够间接拮抗依诺肝素[509]。这些特异性解毒剂的临床应用仍需进一步评估。

9.6.2 存在出血风险或出血事件的心房颤动患者的口服抗凝治疗

虽然应当中断抗凝治疗以控制活动性出血,但出血事件后长期 OAC 的绝对禁忌证是罕见的。当有临

床意义的出血是停止 OAC 的原因时,从一种抗凝药物更换为另一种抗凝药物可能是合理的。大出血事件

的许多原因或诱因是可治疗和/或消除的,包括未控制的高血压、胃肠道溃疡和颅内动脉瘤。在出血事件后

重新启动抗凝治疗通常是临床判断[460,510]。决策是困难的,包括中断和重新使用 OAC,应当由多学科团队

衡量再次卒中和出血的预计风险,考虑出血风险与卒中预防治疗的差异后作出决定。对选定的患者,LAA

切除或封堵可能是一种可行的替代方案。

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出血治疗的推荐

推荐 推荐

类别

证据

水平

参考

文献

应当考虑在合并高血压的抗凝治疗患者中控制血压,以减少

出血风险。 Ⅱa B 511

当使用达比加群时,在>75 岁的患者中可考虑减少剂量

(110mg,每日两次)以减少出血风险。 Ⅱa B 490

在胃肠道出血风险高的患者,VKA 或其它 NOAC 应当优先于

达比加群 150mg 每日两次,利伐沙班 20mg 每日一次或依度

沙班 60mg 每日两次。

Ⅱa B

321,396,402,

405,490,492,

493,512

在所有考虑使用 OAC 的患者中,应当建议避免酒精过量并予

以治疗。 Ⅱa C

不推荐在开始 VKA 治疗前进行基因检测。 Ⅲ

(无益)

B 497

经多学科 AF 团队考虑了不同的抗凝剂、卒中预防措施、改善

了影响出血和卒中风险因素的管理后,对所有合适的患者在

出血事件后,应考虑重新启动 OAC 治疗。

Ⅱa B 460

对于严重活动性出血事件的 AF 患者,推荐中断 OAC 治疗直

至出血原因得以解除。 Ⅰ C

AF:心房颤动; NOAC :非维生素 K 拮抗剂类口服抗凝剂;OAC:口服抗凝剂; VKA:维生素 K 拮抗剂

a:推荐类别

b:证据水平

c:支持推荐的参考文献

9.7 口服抗凝剂和抗血小板药物的联合治疗

在当前的临床试验[513]和注册研究[514-516]中,大约 15%的 AF 患者有心肌梗死病史。5-15%的 AF 患者

在其一生中需要支架治疗。这种情况下,需要仔细考虑抗凝治疗,平衡出血风险、卒中风险和急性冠脉综

合征(ACS)的风险[516]。OAC 和抗血小板治疗的联合处方,尤其是三联治疗,增加大出血的绝对风险

[445,517,581]。最近的一项纳入了 30 866 名近期 ACS 患者的荟萃分析,对 NOAC 加用一种(4135 名患者)或

两种(26731 名患者)抗血小板药物进行了评价[519]。额外加用 NOAC 增加出血风险 79-134%,而仅在没

有 AF 的患者中临界减少缺血事件复发风险。对于 AF 伴有稳定性 CAD,但既往 12 个月内没有 ACS 和/或

冠脉介入治疗的患者中,推荐 OAC 单药治疗,不联合抗血小板药物。对于治疗中的 ACS 患者和植入了冠

脉支架的患者,短期 OAC、氯吡格雷和阿司匹林三联治疗看来是合理的(图 12)。

9.7.1 需要口服抗凝剂治疗的患者在急性冠脉综合征和经皮冠状动脉介入后的抗栓治疗

对接受经皮冠状动脉介入治疗的 AF 患者,最优的抗栓联合治疗或联合疗程尚不明确,但是持续的出

血风险提示疗程要短。工作组审查并重新考虑了专家共识[520],提出以下原则:有卒中风险的 AF 患者、机

械性瓣膜患者和近期或者复发深静脉血栓或肺栓塞的患者,在支架植入期间和植入后应当继续 OAC 治

疗。通常,推荐短期三联治疗(OAC,阿司匹林,氯吡格雷),然后双联治疗一段时期(OAC 加一种抗

血小板药物)(图 13)。当使用一种 NOAC 时,共识推荐对 AF 的卒中预防应考虑使用最低的有效剂量。

目前不推荐减少剂量低于已在Ⅲ期试验中证实的、已得到批准的剂量,这仍有待正在进行的对照试验评

价。不推荐联合使用阿司匹林、氯吡格雷和低剂量利伐沙班(2.5mg,每日两次)用于 AF 患者卒中预防

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[521]。

因为缺乏相应证据,且与氯吡格雷相比,主要出血风险更大,应当避免使用普拉格雷或替格瑞洛作为

三联治疗的一部分,除非明确必需这些药物(如在阿司匹林加氯吡格雷时发生支架内血栓)[522,523]。将

来,正在进行的试验将得到关于这种联合治疗的信息。

在 WOEST(植入了冠状动脉支架的口服抗凝患者,最优化的抗血小板和抗凝治疗是什么?)试验

中,评价了持续氯吡格雷和 OAC 而无阿司匹林的治疗方案,在 573 名接受经皮冠状动脉介入治疗的抗凝

患者(70%伴有 AF)随机分为 OAC 和氯吡格雷(75mg,每日一次)双联治疗或 OAC、氯吡格雷和阿司

匹林三联治疗组[524]。双联治疗组与三联治疗组相比,出血较少,主要是受轻微出血事件影响。心肌梗

死、卒中、靶血管再血管化和支架内血栓发生率没有差异(虽然事件数较低),但是双联治疗组 1 年时的

全因死亡较低(2.5% vs.三联治疗组 6.4%)。尽管试验规模较小,不能评价缺血结局,在将来,OAC 和氯

吡格雷双联治疗组可能作为 AF 合并 ACS 和/或冠脉介入治疗患者三联治疗的替代方案[525]。

口服抗凝剂和抗血小板药物联合治疗的推荐

推荐 推荐

类别

证据

水平

参考

文献

对稳定的冠状动脉性心脏病合并 AF 的患者,在选择性冠脉支架植

入术后,应当考虑阿司匹林、氯吡格雷和一种口服抗凝剂三联治疗

1 个月以预防冠状动脉和脑缺血事件复发

Ⅱa B 522,

524

在有卒中风险的 AF 患者急性冠脉综合征植入支架后,应当考虑阿

司匹林、氯吡格雷和一种口服抗凝剂三联治疗 1-6 个月以预防冠状

动脉和脑缺血事件复发。

Ⅱa C 520

在有卒中风险的 AF 患者发生急性冠脉综合征,但未植入支架,应

当考虑一种口服抗凝剂和阿司匹林或氯吡格雷双联治疗至 12 个月

以预防冠状动脉和脑缺血事件复发。

Ⅱa C

联合抗栓治疗的持续时间,尤其是三联治疗,应当限制在一定时间

内,同时权衡冠脉事件再发和出血的预期风险。 Ⅱa B 520

对于选择的患者,可以考虑用任何一种口服抗凝剂加氯吡格雷

75mg/日的双联治疗作为初始三联治疗的替代方案。 Ⅱb C

524,

525

ACS:急性冠脉综合征;AF:心房颤动; OAC:口服抗凝剂; VKA:维生素 K 拮抗剂

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10. 心房颤动的心室率控制治疗

室率控制是 AF 患者管理不可或缺的部分,充分的室率控制常能改善 AF 相关症状。与卒中预防和节

律控制相比,几乎没有强有力的证据证实室率控制治疗的最佳类型和强度,数据主要来自于短期交叉试验

和观察性研究[41,526-528]。使用β阻滞剂、地高辛、钙拮抗剂地尔硫卓和维拉帕米或联合治疗控制心室率可

以达到紧急或长期室率控制的目的(表 15)。一些抗心律失常药物(胺碘酮、决奈达隆、索他洛尔,以及

普罗帕酮在某种程度上也可以)也有减慢心率的作用,但是它们仅仅用于需要节律控制治疗的患者(见第

11 章)。

10.1 急诊心室率控制

在急性新发 AF 的情况下,患者通常需要控制心率。医师应当评估增加心率的可能原因,如感染、内

分泌失衡、贫血和肺栓塞。对紧急室率控制,β阻滞剂和地尔硫卓/维拉帕米优于地高辛,因为它们能迅速

起效,且对交感张力增高有效[528-532]。药物选择(表 15)和目标心率取决于患者特征、症状、LVEF 和血

流动力学,但是宽松的初始心率目标似乎是可接受的。可能需要联合治疗(表 14)。在 HFrEF 的患者,

应使用β阻滞剂、洋地黄(地高辛或洋地黄毒甙)或其联用[218,533],因为地尔硫卓和维拉帕米在 LVEF<

40%的患者有负性肌力作用[222,534,535]。在病情严重的患者以及严重 LV 收缩功能受损的患者中,当过快的心

率导致血流动力学不稳定时,可静脉内使用胺碘酮[536-538]。对于不稳定的患者应考虑急诊复律(见 11.2

章)。

10.2 长期药物控制心室率

10.2.1 β阻滞剂

β阻滞剂单药治疗通常是室率控制的一线药物[539],主要基于观察性研究中其对紧急室率控制优于地

高辛。有趣的是,在窦性心律的 HFrEF 患者中所见的β阻滞剂预后获益,在 AF 患者中消失了。在一项个

体患者水平 RCTs 的荟萃分析中,基线存在 AF 的患者,与安慰剂相比,β阻滞剂未能降低全因死亡率

(HR 0.97; 95% CI 0.83–1.14; P= 0.73),而窦性心律患者有明确获益(HR 0.73;95% CI 0.67–0.80;

P<0.001)[23]。一项包括 3066 名 HFrEF 合并 AF 的参与者的分析显示,在所有亚组结局一致,在纳入的

10 项 RCTs 研究间没有异质性(I2=0%)。尽管在 HFrEF 患者中没有预后获益,但工作组仍然考虑在所有

AF 患者中β阻滞剂作为一种有用的室率控制的一线药物,这基于室率控制可能使症状和功能得以改善,

已发表的研究中没有有害的证据,且在所有年龄组,无论窦性心律还是 AF 患者均有良好的耐受性[23,540]。

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表 15 心房颤动中的室率控制治疗

治疗 急诊静脉室率控

长期口服室率控制

副作用 评价

β阻滞剂 a

比索

洛尔

未提供 1.25-20mg 一日一

次或分次

报道最常见的不适症状包

括乏力、头痛、外周水

肿、上呼吸道症状、胃肠

道不适和头晕。副作用包

括心动过缓、房室传导阻

滞和低血压

支气管痉挛罕见,对哮喘

病例,推荐β1 选择性药

物(避免卡维地洛)。禁

忌证为急性心力衰竭和严

重的支气管痉挛病史

卡维

地洛

未提供 3.125-50mg 一日两

美托

洛尔

2.5-10mg 静脉推注

(必要时可重复)

每日总剂量 100-

200mg(根据剂

型)

奈必

洛尔

未提供 2.5-10mg 一日一次

或分次

艾司

洛尔

0.5mg 静脉推注 1 分

钟以上,然后 0.05-

0.25mcg/kg/min

钙通道阻滞剂

地尔

硫卓

15-25mg 静脉推注

(必要时可重复)

60mg 一天三次,

最大每日总剂量

360mg(缓释片

120-360mg 每日一

次)

报道最常见的不适症状包

括头晕、不适、乏力、头

痛、潮热、胃肠道不适和

水肿。副作用包括心动过

缓、房室传导阻滞和低血

压(维拉帕米可能伴有长

时间低血压)

与β阻滞剂合用需谨慎。

肝功能损害需减少剂量,

肾功能损害需以小剂量起

始。禁忌证为伴有肺淤血

或 LVEF<40%的左室衰

维拉帕米

2.5-10mg 静脉推注(必要时可重复)

40-120mg 一天三次,(缓释片120-480mg 每日一次)

心脏糖甙类

地高

0.5mg 静脉推注(24

小时内 0.75-1.5mg

分次给予)

每日剂量 0.0625-

0.25mg

报道最常见的不适症状包

括胃肠道不适、头晕、视

物模糊、头痛和皮疹。在

中毒范围内(血清水平>

2ng / mL),地高辛有促心

律失常作用,可能加重心

力衰竭,尤其是合并低血

钾的患者

高血浆浓度增加死亡风

险。在伴有 CKD 的患者

中开始前检测肾功能并调

整剂量。存在旁路、室性

心动过速和伴有流出道梗

阻的肥厚型心肌病的患者

为禁忌证

洋地黄毒甙

0.4-0.6mg 静脉推注

每日剂量 0.05-

0.3mg

特殊适应证

胺碘

300mg 溶于

250mL5%的葡萄糖

中 30-60 分钟静脉点

滴(最好经中心静

脉)b

200mg/日 低血压、心动过缓、恶

心、QT 间期延长、肺毒

性、皮肤变色、甲状腺功

能减退、角膜色素沉积和

伴有渗出的皮肤反应

建议使用联合治疗心室率

控制未达标的患者作为辅

助治疗

AF:心房颤动;CKD:慢性肾病;i.v.:静脉注射;LV:左心室;LVEF:左室射血分数

a:也有一些其他的β阻滞剂,但是不推荐用于 AF 中的特异性室率控制治疗。这包括阿替洛尔(25-100mg 一日一

次,生物半衰期短),普萘洛尔[非选择性,1mg1 分钟以上,间隔 2 分钟可重复最多 3mg(急诊)或 10-40mg,每

日三次(长期)],或拉贝洛尔[非选择性,1-2mg/min(急诊)]

b:如果需要持续使用胺碘酮,24 小时内继以 900mg 溶于 500-1000mL 经中心静脉注射

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10.2.2 非二氢吡啶类钙拮抗剂

在 AF 患者中,维拉帕米或地尔硫卓可达到合理的室率控制目标[541]。它们应避免用于 HFrEF 患者,

因为其具有负性肌力作用[222,534,535]。维拉帕米或地尔硫卓可改善心律失常相关症状[526],与之相比,在一项

合并 LVEF 保留的低危患者的小型试验中,β阻滞剂降低活动能力和增加 B 型钠尿肽水平[542]。

10.2.3 洋地黄

心脏糖甙类,如地高辛和洋地黄毒甙的使用已经超过两个世纪,尽管在过去 15 年里处方量稳步下降[543]。在随机化洋地黄研究组试验(DIG)中,对窦性心律的 HFrEF 患者,与安慰剂相比,地高辛对死亡

率没有影响((RR 0.99; 95% CI 0.91–1.07),但可降低入院率(RR 0.72;95% CI 0.66–0.79)[544,545]。地

高辛治疗 AF 患者没有头对头的 RCTs 研究[546]。观察性研究发现使用洋地黄的 AF 患者伴有死亡增加[547-

549],但是这种关联似乎是由于选择偏倚和处方偏倚而不是由地高辛引起的[550-553],尤其是在病情更重的患

者中更常处方地高辛[225]。在一项纳入 47 名 HFrEF 伴有 AF 患者的交叉试验中,心率、血压、行走距离及

LVEF 在卡维地洛和地高辛组无差异,尽管β阻滞剂导致较高的 B 型利钠肽水平,但联合使用卡维地洛/地

高辛可改善 LVEF,而停用地高辛可减少 LVEF[554]。相较于其他基于小型短期研究的室率控制治疗方法,

与地高辛相比,运动能力、生活质量或 LVEF 没有或仅有轻微差异[526,554-558]。较低剂量的地高辛(每日≤

250μg),血清地高辛浓度为 0.5-0.9ng/mL,可能伴有较好的预后[225]。

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10.2.4 胺碘酮

胺碘酮作为最后一种手段对室率控制可能是有用的。胺碘酮伴随的多种心外副作用使其仅作为联合治

疗(如β阻滞剂或维拉帕米/地尔硫卓和地高辛的联合治疗)不能控制室率患者的备选药物。

总之,在 AF 中使用不同的室率控制药物需要一个平衡。应当在个体化的基础上,在考虑患者特征和

患者意愿后,确定选择β阻滞剂、地尔硫卓/维拉帕米、地高辛还是联合治疗。所有可提供的治疗均有潜在

副作用,治疗应当从低剂量开始,逐渐向上滴定剂量以达到症状改善。在临床实践中,达到心率<110bpm

通常需要联合治疗(图 15)。不同室率控制策略在症状、生活质量和其他中间终点的获益正在研究中[559]。

10.3 心房颤动患者的心率控制目标

AF 患者的最佳心率目标尚不清楚。RACE(永久性心房颤动中室率控制的效果)Ⅱ研究对 614 名永久

性 AF 患者进行了随机,分为静息心率<80bpm,中等运动时心率<110bpm 组,以及宽松目标心率<

110bpm 组。临床事件[560]、NYHA 分级或住院率的复合终点[560,561]没有差异(严格心率控制组为 14.9%,

宽松心率控制组为 12.9%)。相似的发现见于 AFFIRM(心房颤动节律管理的随访研究)和 RACE 试验

(1091 名参与者)的汇集分析 [562],尽管在心率上有很小的差异且没有随机。值得注意的是,一些“充分

心率控制”的患者(静息心率 60-100bpm)有严重症状,需要额外治疗[194]。虽然如此,宽松的心率控制是

可接受的初始目标,无论心力衰竭状态如何,除非症状需要更严格的心率控制。

10.4 房室结消融和起搏

当药物控制心室率和症状失败时,消融房室结/希氏束并植入 VVI 起搏器可以控制心室率。这一操作

相对简单,且并发症率和长期死亡风险低[563,564],尤其是当 AV 结消融前几周植入起搏器,且在消融后初

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始起搏频率设定在 70-90bpm 时[565,566]。这一操作不会使 LV 功能恶化[567]。在经选择的双室起搏治疗(心脏

再同步化治疗)的 HFrEF 患者中,AF 可能终止[571],尽管心脏再同步化治疗的这种“节律控制”效果似乎

很小且尚需证实[572]。AV 结消融使得患者余生需要依赖起搏器,故 AV 结消融和起搏仅限于那些通过室率

控制药物或合理的节律控制措施(见 AF 心脏团队,第 12 章)不能改善症状的患者。起搏治疗的选择(带

有或不带有植入性除颤器的右室或双室起搏)应取决于患者的个体特征,包括 LVEF[573,574]。

心率控制的推荐

推荐 推荐

类别

证据

水平

参考

文献

推荐β阻滞剂、地高辛、地尔硫卓或维拉帕米用以控制 LVEF≥

40%的 AF 患者的心室率。 Ⅰ B

225,526,52

8,531,532,5

41,555,575

推荐β阻滞剂和/或地高辛、地尔硫卓或维拉帕米用以控制

LVEF<40%的 AF 患者的心室率。 Ⅰ B

23,225,526,

533,554,

575,576

如果单药治疗不能达到必要的目标心率,应当考虑不同的室率

控制药物联合治疗。 Ⅱa C 23,554,577

在血流动力学不稳定或 LVEF 严重受损的患者,可以考虑胺碘

酮用于急诊心率控制。 Ⅱb C 536-538

在永久性 AF 的患者(如没有计划尝试恢复窦性心律),抗心

律失常药物不应常规用于室率控制。

(有害) A 41,578,579

在室率控制治疗时,应当考虑静息心率<110bpm(即宽松的心

率控制)作为初始的心率目标。 Ⅱa B 560

在预激性 AF 和妊娠期 AF 中,应考虑节律而不是室率控制策

略作为优先治疗方案 Ⅱa C 486

对强化室率控制和节律控制无反应或不能耐受的患者,应考虑

房室结消融用以控制心率,需接受这些患者将成为起搏器依赖

者。

Ⅱa B 184,564,

569

AF:心房颤动;bpm:次/分;LVEF:左室射血分数

当可提供时,洋地黄毒甙是地高辛的合适替代药物。在伴有射血分数降低(LVEF<40%)的心力衰竭患者,推荐的

β阻滞剂是比索洛尔、卡维地洛、长效美托洛尔和奈必洛尔

11. 心房颤动节律控制治疗

恢复和保持窦性心律是 AF 管理不可或缺的一部分。抗心律失常药物维持窦性心律的作用大约是安慰

剂的两倍[580-584]。当抗心律失常药物无效时,导管消融或联合药物治疗通常是有效的[226,585-587]。尽管许多

临床学家相信维持窦性心律能够改善 AF 患者的转归[588],但是所有比较节律控制与室率控制的试验证实,

单独室率控制(联合适当的抗凝药物)导致中性结果[41,578,579,582,589-593]。目前针对是否包括导管消融、联合

治疗和早期治疗在内的现代室率控制治疗,能否减少主要心血管事件仍在研究中,如 EAST-AFNET4(早

期治疗心房颤动预防卒中试验)[40]和 CABANA(导管消融与抗心律失常药物治疗房颤的试验)[594]试验。

现在,对于充分的室率控制治疗后仍有症状的 AF 患者,节律控制治疗对改善症状有指征。

11.1 急诊转复为窦性心律

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11.1.1 抗心律失常药物急诊转复窦性心律(药物复律)

小规模对照试验、荟萃分析[41,584,595,596]以及一些大型对照试验均已证实,抗心律失常药物能够恢复 AF

患者的窦性心律(药物复律)[597-605]。在欧洲之外,多非利特可提供,可转复新发 AF[606]。药物复律能将

大约 50%的新发 AF 患者转复为窦性心律(表 16)[607-609]。短期内,电复律比药物转复更快更有效,并且

住院时间短[609-613]。而药物转复不需要麻醉或空腹(图 16)。

氟卡尼和普罗帕酮是有效的复律药物[595,602-605,614,615],但是它们仅限于没有结构性心脏病的患者,当可

提供时,伊布利特是一种替代药物,但其有尖端扭转型室速的风险[615]。维纳卡兰[602-605]可用于轻度心力衰

竭的患者(NYHA Ⅰ或Ⅱ级),包括缺血性心脏病患者,只要他们不伴有低血压或严重主动脉瓣狭窄[616-

618]。胺碘酮可用于心力衰竭患者以及缺血性心脏病患者(尽管在大多数 AF 转复试验中排除了严重心力衰

竭患者)[596]。在静脉用药 8-12 小时之后,胺碘酮还能减慢心率 10-12bpm[596]。在恢复窦性心律方面,胺

碘酮和氟卡尼均显示比索他洛尔更为有效[600,601,619]。

11.1.2 患者自行用“口袋中的药片”复律

在特定的症状发作不频繁的阵发性 AF 患者中,已在医院确认安全后,可由患者在家中自行服用单剂

量氟卡尼(200-300mg)或普罗帕酮(450-600mg)(Pill in the pocket)以恢复窦性心律[620]。与院内复律

相比,这一方法似乎效果稍低[621],但具有实用性,且在特定患者中能够控制并提供保证。

11.1.3 电复律

同步直流电复律能够迅速有效地将 AF 转复为窦性心律,是伴有严重血流动力学受损的新发 AF 患者

首选的方法(图 16)[626-628]。电复律在予以静脉咪达唑仑和/或丙泊酚麻醉的患者中能够安全进行。在操作

过程中持续监测血压和血氧是重要的[629]。偶尔可观察到皮肤灼伤。应备用静脉阿托品或异丙肾上腺素,

或者经皮临时起搏以用于复律后心动过缓。双向波除颤器比单向波更为有效,已成为厂家的标准配置[626,628]。与前侧位放置电极板相比,前后位电极板对左心房可产生更为有力的电击区域,恢复窦性心律更

为有效[626,627,630]。

预先使用胺碘酮(需要数周)、索他洛尔、伊布利特或维纳卡兰治疗,可改善电复律效果,而氟卡尼[584]和普罗帕酮可有相似的效果[635]。β阻滞剂[636]、维拉帕米,地尔硫卓[637-639],和地高辛[640,641]不能可靠

地终止 AF 或有利于电复律。当转复后计划用抗心律失常药物治疗维持窦性心律时,在转复前 1-3 天开始

药物治疗(胺碘酮要数周)是明智的,以促进药物转复和达到有效的药物水平[584,601]。

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表 16 用于药物复律的抗心律失常药物

药物 用药

途径

首次剂量 后续剂量 风险 参考

文献

氟卡尼 口服

IVa

200-300mg

1.5-2mg/kg10

分钟以上

N/A 低血压、心房扑动伴 1:1 传

导,QT 延长。避免用于 IHD

患者和/或明显结构性心脏病患

595,598

胺碘酮 IV 5-7mg/kg1-2

小时以上

50mg/小

时,最大

24 小时

1.0g

静脉炎、低血压、心动过缓

/AV 阻滞。减慢心室率。延迟

转复为窦性心律(8-12 小

时)。

596,601

普罗帕

IV

口服

1.5-2mg/kg10

分钟以上

450-600mg

低血压、心房扑动伴 1:1 传

导,QRS 延长(轻度)。避免

用于 IHD 患者和/或明显结构

性心脏病患者

622,625

伊布利

特 b

IV 1mg 10 分钟

以上

10 分钟

后,1mg 10

分钟以上

QT 延长、多形性室速/尖端扭

转型室速(3-4%的患者)。减

慢心室率。避免用于 QT 间期

延长、低血钾、严重 LVH 或射

血分数降低患者。

614,615

维纳卡

IV 3mg/kg10 分

钟以上

15 分钟

后,2mg/kg

10 分钟以

低血压、非持续性室性心

律失常、QT 和 QRS 延长。

避免用于 SBP<100mmHg、近

期(<30 天)ACS、NYHAⅢ

和Ⅳ级心力衰竭、QT 间期延

长(未校正的 QT>440ms)和

严重主动脉瓣狭窄的患者

602-

605,618

ACS:急性冠脉综合征;AV:房室的;IHD:缺血性心脏病;i.v.:静脉注射;LVH:左室肥

厚;NYHA:纽约心脏病学会。

a:使用大的外周静脉,在 24 小时内将 i.v.(中心静脉)给药改为口服给药。

b:伊布利特仅在欧洲某些国家可提供。

11.1.4 复律患者的抗凝治疗

在未抗凝的患者中,复律存在固有的卒中风险[642],可通过予以抗凝剂大大减少这种风险[643]。在所有

计划复律的患者中,即刻开始抗凝是重要的[644-646]。AF 超过 48h 的患者应当在复律前开始 OAC 治疗至少

3 周,复律后持续用 4 周(对于没有长期抗凝需要的患者)。在有卒中风险的患者中,OAC 应当长期应

用。这一措施没有经过对照试验进行评估,但是根据芬兰的大规模观察性数据中似乎是安全的[647]。需要

早期复律时,TOE 能够排除绝大多数左心房血栓,可以进行即刻电复律[648,649]。正在进行的研究将告诉我

们在计划复律的患者中使用 NOACs 开始抗凝的安全性和有效性。

11.2 长期抗心律失常药物治疗

抗心律失常药物治疗的目标是改善 AF 相关症状[41,580]。因此,开始长期抗心律失常药物治疗的决定需

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要权衡症状负荷、可能的药物不良反应和患者意愿。在 2010 年 ESC AF 指南中列出的抗心律失常药物治疗

的原则[369]仍然适用,并应当观察:

(1) 治疗旨在减轻 AF 相关症状;

(2) 抗心律失常药物维持窦性心律的效果是适度的;

(3) 临床成功的抗心律失常药物治疗可减少而不是消除 AF 复发;

(4) 如果一种抗心律失常药物治疗“失效”,使用另一种药物可能达到临床可接受的效果;

(5) 药物的致心律失常作用或心外副作用常见;

(6) 应当首先考虑安全性而不是有效性来指导抗心律失常药物选择

与不治疗相比,抗心律失常药物维持窦性心律的效果大约提高一倍[580]。节律控制治疗对死亡或心血

管并发症没有影响,但轻度增加住院风险(通常是因为 AF)[41,578,579,582,589-593]。为减少副作用风险[201,580],

短期抗心律失常药物治疗似乎是值得的。举例来说,与长期治疗相比,在 AF 复律后用氟卡尼短期治疗(4

周)耐受性良好,且能预防大多数(80%)AF 复发[584]。短期抗心律失常药物治疗也能用于避免导管消融

后 AF 早期复发[650],在那些被认为抗心律失常药物副作用风险增加或预期 AF 复发风险低的患者可能是合

理的。

除抗心律失常药物治疗和导管消融外(见 11.3 节),合并心血管疾病的治疗可以降低 AF 症状负荷,

有利于窦性心律的维持[203,204,296,312]。这包括减低体重、控制血压、治疗心力衰竭、增加心肺适应性和其他

措施(见第 7 章)。

11.2.1 长期抗心律失常药物治疗的选择:安全第一!

通常,抗心律失常药物的安全性决定了首选的抗心律失常药物(图 17)。以下主要抗心律失常药物可

用于预防 AF:

11.2.1.1 胺碘酮

胺碘酮是一种有效的多通道阻滞剂,降低心室率,且在心力衰竭患者中是安全的[582,651]。可能发生促

心律失常作用,引起尖端扭转型室速,在治疗中应当监测 QT 间期和 TU 波(见表 17)[652]。胺碘酮经常引

起心外副作用,尤其是在长期治疗时[653,654],这使其在适用其他抗心律失常药物的患者中限于二线治疗。

可能由于其生物半衰期较长,胺碘酮不太适合于间断的短期治疗(除非是在导管消融后)[655]。

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11.2.1.2 决奈达隆

在至少有一种心血管合并疾病的阵发性和持续性 AF 或心房扑动患者中,决奈达隆可维持窦性心律、

降低心室率、预防心血管住院(大多数是由于 AF)以及心血管死亡[583,588,656]。在近期失代偿性心力衰竭的

患者中(有或没有 AF)[656],决奈达隆增加死亡率,在永久性 AF 患者中,不能使其恢复窦性心律[658]。决

奈达隆中度增加血清肌酐,反映了肌酐排泄减少而不是肾功能下降 [659]。

11.2.1.3 氟卡尼和普罗帕酮

氟卡尼和普罗帕酮对预防 AF 复发有效[581,584,620]。它们仅用于没有明显缺血性心脏病或心力衰竭的患

者,以免发生危及生命的室性心律失常[660]。氟卡尼或普罗帕酮将 AF 时转为心房扑动时 1:1 传导导致的快

速心室率可事先使用β阻滞剂、维拉帕米或地尔硫卓预防。

11.2.1.4 奎尼丁和丙吡胺

在 1 年随访时,奎尼丁和丙吡胺均伴随有全因死亡的增加(OR 2.39;95% CI 1.03–5.59,每治疗 109

例发生 1 例事件,95% CI 34–4985)[580,661],很可能是由于室性心律失常(尖端扭转型室速)所致[580,661]。

尽管这一促心律失常作用在较高剂量时更常见,但它们很少用于 AF 的节律控制。丙吡胺对“迷走神经介

导的”AF(如运动员和/或在睡眠期间发生的 AF[76])可能更有用,并且显示能够降低 LV 流出道压力阶

差,改善肥厚型心肌病患者的症状[662-664]。

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11.2.1.5 索他洛尔

索他洛尔有发生尖端扭转型室速的风险[在复律后心房颤动预防试验(PAFAC)中为 1%[118]]。在心肌

梗死后 LV 功能不良的患者中,与安慰剂相比,索他洛尔的 d 异构体伴有死亡增加[665],可能是由于室性心

律失常所致(OR 2.47;95% CI 1.2–5.05;每治疗 166 例发生 1 例事件; 95% CI 61–1159)[580,665]。另一方

面,在两项对照试验中,d、l-索他洛尔用于 AF 患者没有安全性警示[581,601]。

11.2.1.6 多非利特

多非力特是另一种钾通道阻滞剂,主要在欧洲之外提供。在心力衰竭患者[666]中,偶尔在对其他抗心

律失常药物无效的患者中,多非利特可恢复和维持窦性心律[667]。

总体说来,限于某些特殊情况下才使用奎尼丁、丙吡胺、多非利特和索他洛尔似乎是明智的。此外,

通常应避免在 AF 患者中联合使用延长 QT 间期的抗心律失常药物进行节律控制(表 17)。

11.2.2 十二导联心电图作为识别存在促心律失常风险患者的工具

识别存在促心律失常风险的患者有助于减少抗心律失常药物的促心律失常风险[668]。除了前述的临床

特征外,在启动抗心律失常药物治疗时,监测 PR、QT 和 QRS 间期能够识别长期治疗中存在药物促心律

失常风险的患者[669-671]。此外,存在“异常 TU 波”是即将发生尖端扭转型室速的征象 [652]。循环分析

ECG 的致心律失常信号,已在近期的抗心律失常药物试验中成功应用[118,584,672]。具体来说,在接受氟卡

胺、普罗帕酮或索他洛尔的患者中,系统地使用 ECG 监测 1–3 天以识别那些存促致心律失常的风险患者[118,584,601]。基于这些评估的实践方法,我们建议在启动抗心律失常药物治疗前,对所有患者记录 ECG。在

启动期间有计划的 ECGs 检查似乎是合理的(表 17)。

11.2.3 新型抗心律失常药物

几种阻滞超速钾电流(IKur)的化合物和其他非典型离子通道抑制剂正在临床研发中[673-675]。目前它们

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尚未用于临床。抗心绞痛药物雷诺嗪,阻滞钾和钠电流并增加葡萄糖代谢,而减少游离脂肪酸代谢,从而

增加氧的利用效率[676,677]。在 MERLIN(雷诺嗪治疗非 ST 段抬高性急性冠脉综合征降低心肌缺血的代谢效

率)试验中,雷诺嗪对非 ST 段抬高性心肌梗死和不稳定性心绞痛是安全的[678]。在一篇对随机化后头 7 天

获得的连续 ECG 记录的事后分析中,与安慰剂组患者相比,随机到雷诺嗪组 AF 发作有减少的趋势

[75(2.4%) vs. 55 (1.7%) 名患者;P =0.08] [679]。在 HARMONY(评估单独或联合应用雷诺嗪和决奈达隆治

疗阵发性心房颤动患者效果的研究)试验中,在 134 名有阵发性 AF 并植入双腔起搏器的受试者中,联合

应用最大测试剂量的雷诺嗪(750mg,每日两次)和决奈达隆(225mg,每日两次),可轻度减少 AF 负荷[680]。几项小型开放标签研究表明雷诺嗪可能增加胺碘酮复律的抗心律失常效果[681-683],而来自于雷诺嗪和

联合使用雷诺嗪-决奈达隆预防植入起搏器的患者中 AHRE 的对照试验,结果则模棱两可[684]。当前,没有

充分证据推荐雷诺嗪作为抗心律失常药物,无论是单独或联合其他抗心律失常药物使用。值得注意的是,

用于心绞痛和心力衰竭的“If通道阻滞剂”伊伐布雷定,增加 AF 风险[685]。

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表 17 用于复律后维持窦性心律的口服抗心律失常药物

药物 剂量 主要禁忌证和警示 需要停

的警示征象

减慢 AV

结传导

建议启

动时

ECG

监测

胺碘酮 每日 600mg 分

次口服 4 周,

400mg 口服 4

周,然后每日

200mg

当与延长 QT 的药物联合治疗,以及在

有 SAN 或 AV 结和传导系统疾病的患

者中应慎用。VKAs 和洋地黄剂量应当

减少。

增加他汀肌病风险。有肝病的患者应

慎用。

QT 延长>

500ms

AF 时为

10-12bpm

基线,1

周,4

决奈达隆 400mg 每日两

NYHA Ⅲ或Ⅳ级,或不稳定性心力衰

竭,与延长 QT 的药物或强 CYP3A4 抑

制剂(如维拉帕米、地尔硫卓、咪唑类

抗真菌药物)联合治疗,以及 CrCl <

30mg/mL 为禁忌证。洋地黄、β阻滞

剂和某些他汀应当减少剂量。常见血

肌酐升高 0.1-0.2mg/dL,不代表肾功能

下降。

肝病的患者应慎用。

QT 延长>

500ms

AF 中为

10-12bpm

基线,1

氟卡尼

氟卡尼缓

释剂

100-150mg 每日

两次

200mg 每日一

如果 CrCl<50mg/mL,肝病,IHD 或

LVEF 降低为禁忌证。

存在 SAN 或 AV 结或传导系统病变者

应慎用。CYP2D6 抑制剂(如氟西汀

或三环类抗抑郁药)增加血浆浓度。

QRS 间期较基

线水平增加>

25%

无 基线,

第 1

天,第

2-3 天

普罗帕酮

普罗帕酮

SR

150-300mg 每日

三次

225-425mg 每日

两次

IHD 或 LVEF 降低为禁忌证。

存在 SAN 或 AV 结或传导系统病变

者、肾或肝损伤以及哮喘者应慎用。

增加洋地黄和华法林浓度。

QRS 间期较基

线水平增加>

25%

轻度 基线,

第 1

天,第

2-3 天

d,l 索他

洛尔

80-160mg 每日

两次

存在明显 LV 肥厚、收缩性心力衰

竭、哮喘、QT 延长、低钾血症、

CrCl<50mg/mL 为禁忌证。

中度肾功能受损需要仔细调整剂量。

QT 间期>

500ms,QT 间

期较治疗开始

增加>60ms

与高剂量

阻滞剂相

基线,

第 1

天,第

2-3 天

AF:心房颤动;b.p.m.:次/分;CrCl:肌酐清除率;CYP2D6:细胞色素 P450 2D6;CYP3A4:细胞色素 P450

3A4;ECG:心电图;IHD:缺血性心脏病;LV:左室的;LVEF:左室射血分数;NYHA:纽约心脏病学会;

VKA:维生素 K 拮抗剂

11.2.4 非抗心律失常药物的抗心律失常作用

ACE 抑制剂或 ARBs 治疗 LV 功能不良的患者和高血压伴有 LV 肥厚的患者能够预防新发

AF[219,236,237,246,250,686]。脑啡肽酶抑制剂需要进一步研究,但似乎不增强这种作用[224]。一项丹麦队的队列研

究也表明,与其他抗高血压药物相比,没有并发症的高血压使用 ACE 抑制剂或 ARBs 作为起始治疗,可

减少 AF 发生率[245]。在没有结构性心脏病的患者,ARB 治疗并不减少 AF 负荷[241]。因此,ACE 抑制剂或

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ARBs 似乎没有直接的抗心律失常效果。然而,在电复律后,在抗心律失常药物的基础上加用 ACE 抑制剂

或 ARB,以减少 AF 复发可能是合理的[248,249,687]。

与安慰剂相比,对于窦性心律的 HFrEF 患者,β阻滞剂治疗可降低新发 AF 风险[23]。也有报道β阻滞

剂可减少症状性 AF 复发[580,636,688],但是这一发现可能受到室率控制获益的影响,这会使更多的 AF 发作无

症状。

在一些小规模 RCTs 中,显示围术期他汀治疗能减少术后 AF 风险[689,690];然而,一项有充分把握度的

安慰剂对照试验显示,围术期瑞舒伐他汀治疗对术后 AF 发作没有效果[691]。他汀治疗也不能预防其他情况

时的 AF[692,693]。同样,也未能证实多不饱和脂肪酸能够获益[241,694-698]。在 AF 管理中,醛固酮受体拮抗剂

的作用尚未在人体广泛研究。尽管依普利酮试验的初步证据鼓励其用于一级预防[243],但当前并没有有力

的证据对醛固酮拮抗剂用于 AF 的二级预防作出推荐[699-701]。

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节律控制治疗的推荐

推荐 推荐

类别

证据

水平

参考

文献

一般推荐

推荐节律控制治疗用于改善 AF 患者的症状。 Ⅰ B 120,586,601

在进行节律控制治疗的患者中,应当管理心血管危险因素和避免 AF 触发因素,以利于维

持窦性心律。 Ⅱa B

203,204,296,3

12

除非 AF 伴有血流动力学不稳定,应当根据患者和医师意愿指导选择电复律或药物复律。 Ⅱa C

AF 复律

推荐在急性血流动力学不稳定的患者中进行 AF 电复律以恢复心输出量。 Ⅰ B 612,720-704

推荐在有症状的持续性或长程持续性 AF 患者中,AF 复律(包括电复律或药物复律)作为

节律控制治疗的一部分。 Ⅰ B

584,601,627,6

28,648,705

应考虑事先使用胺碘酮、氟卡尼、伊布利特或普罗帕酮治疗以增加电复律成功率并预防 AF

复发。 Ⅱa B

248,584,633

在没有缺血性或结构性心脏病病史的患者中,推荐氟卡尼、普罗帕酮或维纳卡兰用于新发

AF 药物复律。 Ⅰ A

602-

605,614,618,6

22,706,707

在没有缺血性或结构性心脏病病史的患者中,应考虑伊布利特用于 AF 药物复律。 Ⅱa B

在选定的近期发作 AF 且没有明显结构性或缺血性心脏病的患者中,在安全性评价后,应

考虑单次口服剂量氟卡尼或普罗帕酮(“口袋药丸”方法)用于患者自我复律。 Ⅱa B

620,621

在缺血性和/或结构性心脏病患者,推荐胺碘酮用于 AF 复律。 Ⅰ A 597-601

在没有高血压、严重心力衰竭或严重结构性心脏病的患者(尤其是主动脉瓣狭窄)中,可

考虑维纳卡兰作为胺碘酮的替代用于 AF 药物复律。 Ⅱb B

602-

605,616,618

计划 AF 复律患者的卒中预防

在每次 AF 或心房扑动复律前尽快启动肝素或 NOAC 抗凝治疗。 Ⅱa B 708,709

在 AF/心房扑动转复前,推荐进行至少 3 周的有效抗凝治疗。 Ⅰ B 648,708

当计划早期转复时,推荐经食道超声心动图(TOE)排除心脏内血栓替代操作前抗凝。 Ⅰ B 648,708

在明确 AF 持续<48 小时的患者,可以在没有 TOE 的情况下进行早期复律。 Ⅱa B 648

在有卒中风险的患者,根据长期抗凝治疗推荐,复律后应长期抗凝治疗,不考虑复律方法

或是否维持窦性心律。在没有卒中危险因素的患者中,推荐复律后抗凝治疗 4 周。 Ⅰ B

353,710

在 TOE 发现血栓的患者,推荐有效抗凝至少 3 周 Ⅰ C

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在复律前应考虑重复 TOE 以确保血栓溶解 Ⅱa C

长期维持窦性心律/预防 AF 复发的 AAD

选择 AAD 需要仔细评估,考虑存在的合并疾病、心血管危险和潜在的严重致心律失常作

用、心外毒性作用、患者意愿和症状负荷。 Ⅰ A

41,580

推荐决奈达隆、氟卡尼、普罗帕酮或索他洛尔用于预防左室功能正常、没有病理性左室肥

厚患者症状性 AF 的复发。 Ⅰ A

581,583,584,5

88,601

推荐决奈达隆用于预防没有心力衰竭的稳定性冠心病患者症状性 AF 的复发。 Ⅰ A 583,588

推荐胺碘酮用于预防心力衰竭患者症状性 AF 的复发。 Ⅰ B 596-598

在预防 AF 复发方面,胺碘酮比其他 AAD 更为有效,但是其心外毒性作用更常见且随时

间而增加。因此,应首先考虑其他 AAD。 Ⅱa C

596-598

AAD 治疗的患者,应进行定期评估以确认其治疗适宜性。 Ⅱa C

583,588,657,6

58,660

应当考虑在 AAD 治疗开始时记录 ECG 以监测心率,检测 QRS 和 QT 间期延长和 AV 阻滞

的出现。 Ⅱa B

582-

584,588,601

不推荐长 QT 间期(>0.5s)或有明显窦房结病变或 AV 结功能不良,而未植入功能性永久

起搏器的患者接受 AAD 治疗。

(有害) C

在拒绝 AF 消融或不是消融适应证的患者中,药物治疗诱发或加重窦房结功能不良时应考

虑心房为基础的起搏治疗以使其能够继续 AAD 治疗。 Ⅱa B

711,712

当可能存在复发时,在 AF 消融后的空白期后应考虑继续 AAD 治疗以维持窦性心律。 Ⅱa B 713

非抗心律失常药物的抗心律失常作用

在心力衰竭合并射血分数降低的患者,应考虑使用 ACEIs、ARBs 和β阻滞剂以预防新发

AF。 Ⅱa A

23,219,236,23

7,239,250,714

在高血压,尤其是伴有 LV 肥厚的患者,应考虑使用 ACE-Is、ARBs 和β阻滞剂以预防新

发 AF。 Ⅱa B

238,246,686,7

14

在复发 AF 接受电复律并使用抗心律失常药物的患者,可以考虑使用 ACE-Is 或 ARB 预先

治疗。 Ⅱb B

236,237,248,2

49

不推荐 ACE-Is 或 ARBs 用于轻微或没有基础心脏病的阵发性 AF 患者的二级预防。 Ⅲ

(有害) B

241,697

ACE:血管紧张素转换酶;AF:心房颤动;ARB:血管紧张素受体拮抗剂;CHA2DS2-VASc:心力衰竭,高血压,年龄≥75 岁(2 分),

糖尿病,卒中(2 分),血管疾病,年龄 65-74 岁和性别(女性);ECG:心电图;LV:左心室;LVH:左室肥厚;NOAC:非维生素 K

拮抗剂类口服抗凝剂;TOE:经食道超声心动图

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11.3 导管消融

自从第一次描述肺静脉触发灶启动阵发性 AF 以来[108],AF 导管消融已从一种特殊的、专业性操作发

展为预防复发性 AF 的普通治疗[587,715]。这主要是通过隔离肺静脉达到目的,可能需要完全的隔离以达到充

分效果[716],并可能需要对左房后壁进行额外消融。AF 消融,当在有经验的中心由经过充分训练的团队进

行时,比抗心律失常药物维持窦性心律更为有效,并发症发生率尽管不可忽略,但与抗心律失常药物的并

发症发生率相似[585,717]。

11.3.1 适应证

导管消融 AF 对有症状的阵发性、持续性 AF 患者恢复和维持窦性心律有效,对长程持续性 AF 消融可

能也有效,但一般作为抗心律失常药物治疗失败或不能耐受之后的二线治疗。在这类患者中,导管消融比

抗心律失常药物治疗更为有效[185,586,713,717-720]。作为阵发性 AF 的一线治疗,随机化试验显示与抗心律失常

药物相比,导管消融仅能轻微改善节律控制效果[585,721-723]。并发症发生率相似,当在有经验的中心进行消

融时,导管消融在特定的要求介入治疗的阵发性 AF 患者中作为一线治疗是合理的。导管消融治疗持续性

或长程持续性 AF 患者的安全性和有效性数据很少,但是无论是否心脏复律,与抗心律失常药物相比,导

管消融后复发率均较低(网络图 2)[185,717,723-726,1039]。在尽管使用了抗心律失常药物仍有症状性 AF 复发的

患者中,所有的 RCTs 均显示,导管消融维持窦性心律优于抗心律失常药物[586,713,727,728]。目前没有迹象表

明,导管消融可预防心血管不良结局(或期望停用抗凝药物)或降低住院率[40,594]。

11.3.2 技巧和技术

对导管消融而言,心房水平完全性肺静脉隔离(PVI)是最佳的记录靶点[716,729-731],可通过逐点的射

频消融,环肺静脉线性损伤或冷冻消融达到,其结果相似[732-734]。完全的肺静脉隔离与不完全隔离相比,

节律控制结果较好[716]。PVI 首先在阵发性 AF 患者中进行了尝试,但是也显示在持续性 AF 中,其效果不

劣于更广泛的消融[729,735]。更为广泛的消融用于持续性 AF 患者,但是目前没有充分数据指导其应用[117,718,719,735-737]。扩展消融操作(在 PVI 基础上)均需要更长的操作时间和接受更多的电离辐射,可能给患

者带来风险。PVI 术后左心房大折返性心动过速相对少见(≈5%)。在冷冻消融中似乎罕见[734],但是在

左心房基质改良消融的患者中发生可能高达 25%,通常是由于消融线不完全所致。因此,对持续性 AF 患

者,复杂碎裂电位消融、转子消融或常规线性消融或其他额外消融对首次消融似乎并不合适 [735,738,739]。然

而,在首次消融后复发 AF 的患者中可以考虑在完全 PVI[716]基础上的额外消融[719,740,741]。在记录到右房峡

部依赖性心房扑动的患者接受 AF 消融时,推荐右房峡部消融。在几个报告进行了评价后,腺苷试验用以

识别需要额外消融的患者仍然是有争议的[739,742-744]。在体表标测或心内膜标测引导下的所谓“转子消

融”,仍然需要评估,目前不推荐常规临床应用。

11.3.3 转归和并发症

11.3.3.1 心房颤动导管消融的转归

在个体患者的 AF 导管消融后,其节律如何是难以预测的[173,227,713,728]。大多数患者为实现症状控制需

要多次消融[713,726,728]。通常,在 AF 病史较短、发作频繁、AF 发作时间短、没有明显器质性心脏病的较年

轻患者中,节律控制更好,手术相关并发症较低[745]。在维持窦性心律方面,导管消融比抗心律失常药物

更有效(网络图 2)[746,1039]。70%的阵发性 AF 和约 50%的持续性 AF 患者消融后,能维持窦性心律,没有

严重症状性 AF 复发[713,728,735]。在维持窦性心律数年后 AF 的极晚期复发并非少见,可能反映了疾病进展,

是需要继续 AF 治疗的重要提示[728]。多个变量被确认为 AF 导管消融术后复发的危险因素,但是它们的预

测强度均不足。因此,导管消融的决定,应当基于共同决策过程[747](见第 8 章),对病人详细解释潜在

的获益和风险、诸如抗心律失常药物的替代方案,或如果不进行节律控制治疗能够接受当前的症状[175]。

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11.3.3.2 心房颤动导管消融的并发症

在临床实践中,全面减少并发症对改善 AF 消融质量是必需的[175]。作为欧洲观察研究计划(EORP)

的一部分,接受首次消融患者的中位住院时间为 3 天(四分位差 2-4 天),这是从来自于每年至少 50 例消

融的医院的 1391 名患者资料中得出的。在 AF 消融后,5-7%的患者会发生严重并发症,2-3%的患者会发

生危及生命、但通常是可治疗的并发症[727,748-750]。有消融中死亡的报道,但很罕见(<0.2%)[751]。最重要

的严重并发症是卒中/TIA(<1%),心脏压塞(1-2%),肺静脉狭窄,以及严重食道损伤,在消融后数

周可致心房食道瘘(表 18)。在大约 10%的射频或冷冻消融的患者中可观察到“沉默型卒中”(如脑

MRI 检测到的白质损伤)[752]。其临床相关性尚不清楚[749]。消融后并发症包括在第一周内风险最高的卒中[753]、消融后数天晚发的心脏压塞[751]、以及通常在消融后 7-30 天显现的食道瘘。及时发现心房食道瘘可挽

救生命,应当根据没有明确原发灶的感染、胸痛后疼痛和卒中或 TIA 的典型三联征进行诊断[748]。

表 18 心房颤动导管消融相关并发症

并发症严重性 并发症类型 发生率 727,748,750,754,759

危及生命的并发症 围术期死亡 <0.2%

食道损伤(穿孔/瘘)a <0.5%

围术期卒中

(包括 TIA/空气栓塞)

<1%

心脏压塞 1-2%

严重并发症 肺静脉狭窄 <1%

持续膈神经麻痹 1-2%

血管并发症 2-4%

其他严重并发症 ≈1%

1-2%

意义未知 无症状脑栓塞(沉默型卒中)b 5-20%

射线暴露

TIA:短暂性脑缺血发作

a:在消融后第一周存在非特异性感染征象、胸痛和卒中或 TIA 三联征的患者应怀疑食道瘘。这需要立即治疗。

b:在冷冻消融或射频消融<10%,分阶段射频消融>20%。

11.3.4 抗凝治疗:消融前、消融中和消融后

使用 VKAs 抗凝的患者在消融期间应当继续治疗(INR2-3)[760]。NOACs 抗凝治疗可用于替代华法林[478,761-765]。在有经验的中心,观察性队列中,导管消融期间不中断 NOAC 治疗没有安全性问题[761,763,766,767]。第一个比较消融患者中继续 NOAC 和 VKA 治疗的对照试验招募了大约 200 名患者,其结果

最近已经发表 [768],也发表了几个观察性数据[761,769,770]。在接受 AF 消融的患者中比较不中断 VKA 与

NOAC 治疗的研究正在进行中[如 AXAFA-AFNET 5(在心房颤动导管消融时使用直接 Xa 因子抑制剂阿哌

沙班抗凝:与维生素 K 拮抗剂的比较;NCT0227550)和 RE-CIRCUIT(在肺静脉消融时随机化评估达比

加群酯与华法林:不间断的围手术期抗凝策略;NCT02348723) ]。在消融过程中,应当予以肝素维持激

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活全血凝固时间>300s。在所有患者中,抗凝应当至少维持 8 周。导管消融后血栓栓塞事件的真实发生率

没有进行过系统性研究,卒中风险根据非消融 AF 队列预测。尽管观察性研究表明在 AF 导管消融后最初

几年里卒中发生率相对较低[737,771-776],但仍需考虑 AF 复发的长期风险和消融后患者抗凝的安全性问题。

在没有对照试验数据的情况下,导管消融后 OAC 应当遵循一般的抗凝推荐,无论推测其为何种节律。

11.3.5 心力衰竭患者中的心房颤动消融

与胺碘酮治疗相比,导管消融明显降低 HFrEF 患者的 AF 复发[777]。特定的 HFrEF 合并 AF 的患者在

导管消融后,LV 收缩功能可以恢复(可能提示为心动过速性心肌病)。几个小型试验表明,在 HFrEF 患

者中导管消融后 LV 功能改善[185,226-228,778,779],住院减少,尤其是在以前没有心肌梗死的患者中[780]。需要进

行大型的试验来证实这些发现。在这些患者中可能需要进行导管消融。因此,在 HFrEF 患者中,导管消融

的适应证应当仔细权衡,操作应当在有经验的中心进行。

11.3.6 导管消融后的随访

在导管消融后的随访中,患者和医生应该知道晚期并发症的症状和体征,以便迅速进行治疗(表

18)。患者应当了解导管消融后有症状或无症状的 AF 复发是常见的[119,781,782]。与节律控制治疗的主要目

标一致,在常规医疗护理中,无症状发作通常不应引发进一步的节律控制治疗。在消融后的最初 12 个月

里,患者应当在心律失常专家处就诊一次。在有症状的 AF 复发患者中,应当考虑进一步的节律控制选

择,包括在心脏团队中进行讨论(图 17,图 19)。

11.4 心房颤动外科治疗

11.4.1 伴随进行的心房颤动外科手术

在 30 年前首次进行了 Cox 迷宫手术,它采用“切开和缝合”技术,包括隔离左心房后壁、二尖瓣环

后部连接、三尖瓣环连接、腔静脉连接以及切除 LAA(图 18)[783]。因此,Cox 迷宫术制造了电学迷宫通

道,通过该通道,窦房结冲。

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动能够传导至房室结,同时可预防颤动传导。Cox 迷宫术以及其他通常更为简单的 AF 外科术式主要

用于接受其他开胸心脏外科手术的患者[461,466,784-798]。对这些指南进行的系统性评价中,同时进行 AF 外科

手术与不进行 AF 外科手术相比,发生 AF、心房扑动、房性心动过速机会减少(根据几项 RCTs,RR

1.94;95% CI 1.51–2.49;n = 554)(网络图 3)[1040]。接受 Cox 迷宫手术的患者通常需要起搏器植入(RR

1.69; 95%CI 1.12-2.54; n=1631 来自 17 项 RCTs),在其他结果或并发症方面没有检出差异。纳入了 67389

名接受开胸心脏手术 AF 患者的胸外科医师协会数据库也支持这些发现:同时进行 AF 外科手术不影响死

亡率或主要致残率(调整的 OR1.00,95%CI 0.83–1.20),但是起搏器植入更多(调整的 OR1.26,95%CI

0.83–1.20)[799]。外科手术后 AF 复发的预测因素包括左心房扩大、高龄、AF 病史>10 年以及非阵发性

AF[800-804]。对于 AF 类型,外科 PVI 似乎在阵发性 AF 中更有效[805]。双心房消融模式可能对持续性和长程

持续性 AF 更有效[797,803,806]。在图 19 中列出了对于接受外科手术伴有 AF 相关症状患者的管理推荐,重要

的是 AF 心脏团队的建议并告知患者参与选择。

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11.4.2 单独进行的节律控制外科手术

当今的技术(如双极消融或冷烙术)使得经小切口 Cox 迷宫术更为简便、可重复且可行[786,807,808]。经

胸腔镜双极消融行 PVI 可预防阵发性 AF 复发(1 年后 69-91%不发生心律失常,消融方式见图 18B)[468,809,810],似乎对导管消融无效的患者也有效[811]。胸腔镜消融的平均住院时间为 3.6 至 6.0 天不等[468,812,813]。FAST(心房颤动导管消融与外科消融治疗的比较)试验[468]和另一项小型试验[814]表明在维持窦

性心律方面,胸腔镜 AF 外科手术比导管消融更为有效[468,814],而且也不会引起更多并发症(表 19)[815]。

为提高效果[468,816-818],进行了更广泛的消融,包括在 PVI 间的连线(“盒状消融”)和与二尖瓣环间的连

线[812,819-822]。为改善透壁损伤的产生[716],最近提出了心内膜-心外膜联合消融策略[812,823-825]。尽管同时进

行杂交消融术的初步经验显示这是有前景的,但操作时间和出血并发症发生率较高[812,823]。

表 19 胸腔镜 AF 手术的并发症

并发症 发生率 [468,815,822,826]

转为胸骨切开术 0–1.6%

起搏器植入 0–3.3%

气胸引流 0–3.3%

心包压塞 0–6.0%

短暂性脑缺血发作 a 0–3.0%

a 无症状脑栓塞的发生率不明。

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11.5 治疗失败后的节律控制选择

对于如何治疗导管消融后 AF 复发的患者,没有充分证据支持的明确推荐。消融后 AF 或房性心动过

速早期复发(8 周内发生)可予以复律治疗。许多已发表的接受 AF 消融的患者系列包括了抗心律失常药

物治疗失败的病例。因此,对于在用抗心律失常药物治疗仍有症状复发的患者,考虑消融治疗是合理的。

或者,也可考虑尝试另一种抗心律失常药物。根据这些药物的不同作用和与 AF 消融可能的协同作用,针

对这两种方法既往单独使用无效而联用可能获益的患者,可考虑消融联合抗心律失常药物(“杂交治

疗”,见第 12 章)。室率控制而不做节律控制、外科消融或重复导管消融均可考虑(图 20)。对于首次

治疗失败后仍需要进一步节律控制的患者,患者意愿和当地是否有条件治疗,是重要的考虑。

11.6 心房颤动的心脏团队

考虑到节律控制治疗失败后仍需要或要求进一步节律控制治疗的患者,不同治疗选择上的复杂性,工

作组推荐应当以 AF 心脏团队的建议为依据做出包括 AF 外科治疗或广泛 AF 消融的决定。这也适用于有严

重 AF 症状(EHRAⅢ或Ⅳ级)的患者转向室率控制策略。AF 心脏团队应当由一位有抗心律失常药物治疗

经验的心脏病学家、一位介入电生理专家和一位有经验的心脏外科医生组成,以选择适当的患者、介入或

外科消融技术(图 20)。应当建立这样的 AF 心脏团队,构建一个合作平台,以支持在提供持续照护的医

师和 AF 心脏专家、介入电生理专家和 AF 外科医师之间的持续互动,从而提供优化建议,并最终提高需

要先进和复杂节律控制措施的患者节律管理的效果。

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心房颤动和心房颤动导管消融的推荐

推荐 类别 水平 参考文献

A

在使用抗心律失常药物(胺碘酮、决奈达隆、氟卡尼、普罗帕酮、索他洛尔)

仍有症状性 AF 复发的患者,以及愿接受进一步节律控制治疗的患者,由经

过适当训练的电生理专家操作,在有经验的电生理中心,推荐对症状性阵发

性 AF 患者进行导管消融以改善 AF 症状。

Ⅰ A 585-587,

713,727

B 如果有心房扑动记录或在 AF 消融中发作心房扑动,作为 AF 消融程序的一

部分,应当考虑对常见心房扑动消融以预防心房扑动复发。 Ⅱa B 827

B 在选定的症状性阵发性 AF 患者,考虑患者的选择、获益和风险,可以考虑

导管消融作为一线治疗代替抗心律失常药物,以预防 AF 复发,改善症状。 Ⅱa B 585

B C 在导管消融(ⅡaB)或外科消融(ⅡaC)后,所有患者应接受口服抗凝剂治

疗至少 8 周。 Ⅱa B C 727

C 在有卒中高风险的患者,接受成功的导管消融或外科消融后,应当继续无限

期抗凝治疗以预防卒中。 Ⅱa C

当计划进行 AF 导管消融时,应当考虑在消融期间继续使用口服 VKA(Ⅱ

aB)或 NOAC(ⅡaC)。 Ⅱa B C 760,768

使用射频或冷冻球囊的导管消融应当以隔离肺静脉为目标。

Ⅱa B

585,715,

716,734,

735

当怀疑心动过速性心肌病时,在症状性 AF 合并射血分数降低的心力衰竭患

者,应考虑 AF 消融以改善症状和心脏功能。 Ⅱa C

185,226-

228,720,77

7-779,828

在有 AF 相关心动过缓的患者中,应考虑 AF 消融作为一种策略,以避免起

搏器植入。 Ⅱa C 829,830

在症状性持续性或长程持续性 AF,对 AAD 治疗无效的患者,考虑患者选

择、获益和风险,有 AF 心脏团队支持,可考虑导管或外科消融以改善症状。 Ⅱa C

468,735,

777,831,

832,1040

当导管消融失败时,对症状性 AF 患者,应当考虑微创外科手术行心外膜肺

静脉隔离。对这类患者的决策应当得到 AF 心脏团队的支持。 Ⅱa B

468,812,

819,823

对症状性顽固性持续性 AF 或消融后 AF,AF 心脏团队应当考虑迷宫手术

——可经微创途径,由经过充分训练的术者,在有经验的中心进行——以改

善症状。

Ⅱa C 808,832

在接受心脏外科手术的患者,权衡手术的额外风险和节律控制治疗的获益

后,应考虑进行迷宫手术,最好是双心房迷宫术,以改善 AF 引起的症状。 Ⅱa A

461,466,

790,791,

796,797

在接受心脏外科手术的无症状 AF 患者,可考虑联合进行双心房迷宫术和肺

静脉隔离术。 Ⅱb C

796,797,83

3

AF:心房颤动; NOAC :非维生素 K 拮抗剂类口服抗凝剂; VKA:维生素 K 拮抗剂

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12 杂交节律控制治疗

AF 有许多不同的驱动因素,抗心律失常药物或导管消融仅针对其中一部分因素[96]。因此,尽管支持

其使用的来自于对照研究的证据极少,但联合或“杂交”节律控制治疗似乎是合理的。

12.1 抗心律失常药物和导管消融联合治疗

在消融后通常使用抗心律失常药物 8-12 周以减少导管消融后的 AF 复发,这得到了最近一项对照的试

验支持,与安慰剂相比胺碘酮减少一半的早期复发[650]。没有进行前瞻性研究,但一篇对可用的证据(弱

的)的荟萃分析表明,在导管消融后应用抗心律失常药物治疗的患者中,能够更好地预防 AF 复发[713]。许

多患者在导管消融后使用抗心律失常药物治疗(大多数是胺碘酮或氟卡尼)[587],这对消融后复发 AF 的患

者似乎是合理的选择。对导管消融后需要进一步节律控制治疗的患者考虑使用抗心律失常药物治疗似乎是

常识,但是这仍然需要对照试验来证实。

对于使用氟卡尼、普罗帕酮或胺碘酮治疗期间发生“药物诱发心房扑动”的患者,联合三尖瓣环峡部

消融和抗心律失常药物治疗可以改善节律控制,而不需要左心房消融 [834-836],但从长期来看 AF 复发仍然

是一个需要关注的问题 [837,838]。

12.2 抗心律失常药物和起搏器联合治疗

对于选择的病态窦房结综合征合并 AF 发作时,心室率反应快、需要室率控制治疗的患者,起搏器不

仅能够优化室率控制而且还有助于控制节律[711,712]。此外,当抗心律失常药物治疗引起窦房结功能障碍并

心动过缓时,起搏使上调抗心律失常药物剂量成为可能。这样的策略还没有前瞻性的研究,现有的人群研

究均是高度选择性的[839,840]。一些 AF 诱发心动过缓的患者可能从 AF 导管消融中获益,无需抗心律失常药

物和植入起搏器[829,830]。

13. 特殊情况

13.1 虚弱和“高龄”患者

许多 AF 患者为高龄(如>70 或>80 岁)。没有研究证实在这些“高龄”AF 患者降低心血管风险不

如年轻患者有效。相反,年龄是 AF 患者缺血性卒中最强有力的预测/危险因素[382]。来自于 BAFTA(伯明

翰老年患者心房颤动治疗研究)[362],NOAC 试验[39]以及美国老年人分析(医疗保险)[396]的良好数据支持

对老年病人使用抗凝药物。老年 AF 患者卒中风险更高,因此,与年轻患者相比更可能从 OAC 中获益[841],但在老年人中 OAC 仍然使用不足[220,842]。尽管对 AF 其他治疗选择的证据基础较少,但可提供的数

据支持使用现有的室率和节律控制措施,包括起搏器和导管消融,没有理由歧视老年。老年患者可能存在

多种共病,包括痴呆、跌倒倾向、CKD、贫血、高血压、糖尿病和认知功能障碍。这些情况可能比 AF 相

关症状更多地限制其生活质量。肝肾功能受损、同时应用多种药物,使得药物相互作用和药物副反应更易

发生。为减少这些患者 AF 治疗的并发症,综合的 AF 管理和仔细调整药物剂量似乎是合理的[843]。

13.2 遗传性心肌病、离子通道病和旁路

几种遗传性心脏疾病伴有早发 AF(表 20)。在这些年轻患者中,基础心脏疾病的治疗对 AF 管理是

很重要的(见 ESC 心源性猝死[844]和肥厚型心肌病[845]指南)。

13.2.1 WPW 综合征

预激合并 AF 患者存在经旁路快速传导的风险,导致快速心室率,可能诱发室颤和猝死。在有前传旁

路证据的 AF 患者,推荐导管消融旁路[869,870]。这一操作安全有效,且可作为预防性治疗策略[871,872]。对于

有旁路证据、发生了猝死事件幸存的 AF 患者,推荐急诊旁路导管消融治疗[869]。除症状性心动过速病史、

存在多条旁路以及埃博斯坦畸形外,在自发或诱发的 AF 期间,记录到短预激 RR 间期(<250ms)是

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WPW 综合征猝死的危险标志之一。静脉注射普鲁卡因酰胺、普罗帕酮或阿马林可用于急诊减慢心室率[873,874],而地高辛、维拉帕米和地尔硫卓是禁忌的[875]。静脉注射胺碘酮应慎用,因为有病例报道,在预激

性 AF 患者中静脉注射胺碘酮后,发生了加速性室性心律和心室颤动[876]。

表 20 与心房颤动相关的遗传性心肌病、离子通道病和旁路

综合征 基因 功能改变 AF 发生

参考文献

长 QT 综合征 KCNQ1 IKs ↓ 5-10% 846-850

KCNH2 IKr ↓

SCN5A INa ↑

ANK2 INa、K ↓

其他 多方面效应

Brugada 综合征 SCN5A INa ↓ 10-20% 851-855

GPDIL INa ↓

SCN1B INa ↓

CACAN1C ICa ↓

CACNB2b ICa ↓

其他 其他

短 QT 综合征 KCNQ1 IKs ↑ 高达 70% 853,856-858

KCNH2 IKr ↑

KCNJ2 IK1 ↑

CACNA1C ICa ↓

CACNB2b ICa ↓

儿茶酚胺敏感性

VT

RYR2 肌浆网 Ca2+释放

异常

有变化但常见 859-861

CASQ2

肥厚性心肌病 肌节基因 5-15% 862-864

WPW 综合征 PRKAG 有变化 865

心-手综合征 TBX5 有变化 866

致心律失常性右

室心肌病

几个桥粒基因,基

因位点未知

细胞间机械接触

减少

在有 VTs 的患

者中>40%

867-868

AF:心房颤动;VT:室性心动过速

13.2.2 肥厚型心肌病

AF 是肥厚型心肌病患者最常见的心律失常,累及大约 1/4 的患者[877]。观察性数据强调并发 AF 的肥

厚型心肌病患者卒中风险增高,证实需要 OAC 治疗[878]。虽然有很多 VKAs 治疗的经验,但没有资料表明

NOACs 不能用于这类患者[845]。对于肥厚型心肌病的患者,缺乏室率控制还是节律控制为好的研究。对于

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这类患者的室率控制,β阻滞剂和地尔硫卓或维拉帕米似乎是合理的治疗选择。在没有 LV 流出道梗阻的

患者,洋地黄可以单独或与β阻滞剂联合应用[845]。胺碘酮在肥厚型心肌病合并 AF 的患者中似乎是一种安

全的抗心律失常药物[879],而专家意见丙吡胺治疗有流出道梗阻的患者可能是有益的。AF 消融可有效抑制

症状性 AF 复发 [880-884]。对于拟行手术(如 LV 流出道梗阻或二尖瓣手术)治疗的肥厚型心肌病患者,AF

的手术治疗可能是适宜的,但是经验有限。

13.2.3 离子通道病和致心律失常性右室心肌病

许多离子通道病和遗传性心肌病伴有 AF。在长 QT 综合征或 Brugada 综合征的患者,AF 患病率在 5-

20%不等(表 20)[853,856-858]。包括 AF 在内的疾病表型外显率不同[61,852,885,886]。在这些疾病中,证实心房动

作电位缩短或延长均是 AF 的可能机制。在遗传性心肌病合并 AF 的患者中,考虑使用抗心律失常药物逆

转可疑的离子通道缺陷似乎是合理的(如在长 QT3 综合征使用钠通道阻滞剂 [852],或在 Brugada 综合征使

用奎尼丁[887])。更为重要的是,对于其他方面健康的年轻新发 AF 患者,应当仔细寻找此类遗传性疾病,

包括临床病史、家族史、ECG 表型、超声心动图和/或其他心脏影像学检查。

在所有 AF 患者中,单基因缺陷仅占 3-5%,即使在年轻人群中也是如此[846,848,888-890]。此外,在检测到

的突变和特异性结果或治疗需求方面没有明确关联。因此,不推荐在普通 AF 人群中进行基因检测[77]。其

他指南也提出了对遗传性致心律失常性疾病患者进行基因检测的适应证[844,891]。

遗传性心肌病的推荐

推荐 推荐

类别

证据

水平

参考

文献

WPW 综合征

推荐 WPW 综合征合并 AF 并经旁路快速传导的患者,进行导管

消融旁路以预防心源性猝死。 Ⅰ B 892-894

对心源性猝死幸存的 WPW 患者,推荐立即导管消融旁路。 Ⅰ C 869

经仔细咨询后,对显性旁路合并 AF 的无症状患者应考虑旁路消

融。 Ⅱa B 872,892

肥厚型心肌病

推荐 HCM 合并 AF 的患者终生服用抗凝药物以预防卒中。 Ⅰ B 878

推荐 HCM 合并症状性新发 AF 的患者,通过电转复或药物恢复

窦性心律以改善症状。 Ⅰ

B

845

血流动力学稳定的 HCM 合并 AF 的患者,推荐使用β阻滞剂和

地尔硫卓/维拉帕米进行室率控制。 Ⅰ C 845

HCM 合并 AF 的患者,应考虑治疗 LV 流出道梗阻以改善症状。 Ⅱa B 896

HCM 合并复发性症状性 AF 的患者,应考虑使用胺碘酮以实现

节律控制并维持窦性心律。 Ⅱa C 845,897

遗传性心肌病和离子通道病

AF 患者,如根据临床病史、家族史或心电图表型怀疑有遗传性

心肌病或离子通道病,应考虑行目标基因检测。 Ⅱa A 852

AF:心房颤动; LV:左心室;WPW:预激综合征

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13.3 运动和心房颤动

体力活动促进心血管健康,这转化为 AF 风险降低[898]。因此,体力活动是预防 AF 的基础。剧烈体育

运动,尤其是竞技性运动(>1500h 的耐力运动)[899],可增加生命后期的 AF 风险[900-902],这可能是由于

自主神经张力改变、运动期间容量负荷改变、心房肥厚和扩张所致[903,904]。这导致体力活动和 AF 发生的关

系表现为 U 形曲线[214,898,902,905,906]。在模型中停止训练能够减少 AF[904],减少运动员室性心律失常[907],但

是停止训练对人类运动员中 AF 的作用仍未知。AF 运动员的管理与一般 AF 管理相同,但是需要一些特别

的考虑。临床风险因素将决定是否需要抗凝治疗。使用 OAC 的患者,应避免直接身体接触或容易受伤的

运动。β阻滞剂耐受性不好,且有时是禁用的,地高辛、维拉帕米和地尔硫卓常常不足以减慢运动期间

AF 的心室率。运动员 AF 导管消融的效果与非运动员可能相似[908,909],但是仍需进一步的资料。单剂量口

服药物治疗也可使用[620]。在口服单剂量氟卡尼或普罗帕酮后,只要 AF 仍持续,患者应当避免运动,直到

抗心律失常药物两个半衰期之后。使用钠通道阻滞剂治疗的运动员,可以考虑对心房扑动折返环进行预防

性消融[910]。

对心房颤动患者体力活动的推荐

推荐 推荐

类别

证据

水平

参考

文献

推荐中等程度规律的体力活动以预防 AF,但应告知运动员长期

持续高强度体育运动可能促发 AF。 Ⅰ A

214,898

,900-902,

905,906

在运动员中应考虑 AF 消融以预防 AF 复发。 Ⅱa B 908,909

在每位运动员中应当评估运动时的 AF 心室率(通过症状和/或监

测),应逐步达到室率控制。 Ⅱa C

在服用单剂量氟卡尼或普罗帕酮后,只要 AF 仍持续,患者应当

避免运动,直到抗心律失常药物两个半衰期之后。 Ⅱa C 620

AF:心房颤动;

13.4 妊娠

在妊娠妇女中 AF 罕见,通常与孕前患有心脏病相关。AF 增加母亲和胎儿并发症[911,912]。对先天性心

脏病更好的治疗,可能增加将来妊娠期间 AF 的发病率[913]。心血管专家、产科医师和新生儿专家应密切合

作,对有 AF 的孕妇应作为高危妊娠进行管理。

13.4.1 室率控制

由于缺乏特定的数据,β阻滞剂、维拉帕米、地尔硫卓和地高辛在美国食品和药品管理局妊娠安全性

分类中均为 C 类(获益可能超过风险),但阿替洛尔除外(D 类:存在风险的阳性证据)。应以最低剂

量,最短时间应用。这些药物不致畸,但是易于通过胎盘 [914]。β阻滞剂通常用于有心血管疾病的孕妇

(如妊娠期高血压和先兆子痫的治疗),但是可能引起宫内发育迟缓[915],因此,推荐在妊娠 20 周后进行

生长监测。对母亲和胎儿心律失常,地高辛被认为是安全的[916]。评价维拉帕米或地尔硫卓的资料不足,

因此推荐使用β阻滞剂和/或地高辛进行室率控制[917]。对于哺乳,所有控制室率的药物均可存在于乳汁

中,β阻滞剂、地高辛和维拉帕米在乳汁中水平均很低,被认为是无害的。地尔硫卓在乳汁中水平高,应

考虑作为二线治疗[918]。

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13.4.2 节律控制

妊娠 AF 患者的节律控制治疗仅有病例研究报道。胺碘酮对胎儿有严重副作用,仅考虑用于紧急情况[919]。氟卡尼和索他洛尔均可用于胎儿心律失常的转复,并且没有严重副作用[920],因此对治疗母体症状性

AF 可能也是安全的。当快速心室率引起血流动力学不稳定时,电复律对恢复窦性心律有效,对母亲和胎

儿的不良事件发生率均很低[921]。然而,考虑到胎儿窘迫风险,电复律应当只有在能够提供胎儿监测设备

和紧急剖宫产的情况下使用。在妊娠期间其他紧急情况,患者应当吸入 100%氧气,早期建立静脉通道,

母亲应当左侧卧位以改善静脉回流[922]。

13.4.3 抗凝治疗

因为存在致畸作用,VKAs 应当避免用于妊娠的前三个月,并避免用于分娩前 2-4 周以免胎儿出血。

低分子肝素是安全的,因为其不通过胎盘[923]。在第三孕期,鉴于一些孕妇需要大剂量 VKA 和肝素以维持

充分抗凝,故建议进行较频繁的实验室检查(如每 10-14 天),并进行相应剂量调整,以保证充分抗凝。

妊娠期有机械瓣的 AF 患者,在妊娠 6-12 周期间,经心脏团队会诊,选择停止 VKA 治疗时,并应当接受

剂量调整的普通肝素持续输注或剂量调整的低分子肝素皮下注射。关于 NOACs 的致畸作用仅有有限的数

据,这些药物应当避免在妊娠期使用。

妊娠期间的推荐

推荐 推荐

类别

证据

水平

参考

文献

在整个妊娠期间,电复律均可安全进行,推荐用于由于 AF 导致血

流动力学不稳定的患者,以及 AF 持续发作对母亲或胎儿风险高的

时候

Ⅰ C

推荐对于有卒中风险的 AF 妊娠患者予以抗凝治疗。为使致畸和宫

内出血风险最低,推荐在妊娠的前三个月和分娩前 2-4 周使用剂量

调整的肝素。维生素 K 拮抗剂或肝素可用于妊娠的其余阶段。

Ⅰ B 923

NOACs 应当避免用于妊娠期及计划怀孕的妇女。 Ⅲ

(有害) C

NOAC:非维生素 K 拮抗剂类口服抗凝剂

13.5 术后心房颤动

心脏外科手术后,AF 很常见(约见于 15-45%的患者)[924-926],伴有住院时间延长、并发症率和死亡

率增高[927]。在其他大手术后,AF 也并不少见,尤其是老年患者。术后 AF 的治疗主要基于对进行了心脏

手术患者的研究,对于非心脏外科手术研究的证据很少。

13.5.1 术后心房颤动的预防

β阻滞剂可降低术后 AF 和室上性心动过速的发生率,尽管在一篇对已发表的研究进行的系统评价

中,存在较高的异质性和中度偏倚。研究最多的药物是普萘洛尔,AF 检出率在治疗组为 16.3%,在对照组

为 31.7%[925]。在大多数研究中,β阻滞剂是在术后给予的,最近的一项荟萃分析支持这一方案[928]。在几

项荟萃分析中,与β阻滞剂治疗相比,胺碘酮降低术后 AF 发生率,还可缩短住院时间[925,929-931]。

尽管有来自于荟萃分析的初步报告[689,932,933],但在一项前瞻性对照试验中,术前予以他汀治疗不能预

防术后 AF[934]。在一些小型假设试验中也研究了其他治疗,但是未能证实明确获益。这些治疗包括镁剂[925,935,936],n-3 多不饱和脂肪酸[937-945],秋水仙碱[946],糖皮质激素[947,948]以及心包后部切除术[949]。尽管有

些研究提示术后超速双心房起搏有预防效果,但其尚未得到广泛应用[925,950]。

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13.5.2 抗凝治疗

术后 AF 伴有早期卒中风险、发病率和 30 天死亡率增高[927,951,952]。从长期来看,与术后窦性心律的患

者相比,有术后 AF 发作的患者心血管死亡率增加两倍,且未来 AF 和缺血性卒中风险大幅增加[952-958]。术

后及术中 AF 患者在出院时予以 OAC 伴有长期死亡率降低[959],但没有对照试验的数据。对于存在卒中风

险高的术后 AF 患者,需要高质量的数据来明确长期抗凝能否预防卒中[368,836],并评价术后短时间 AF 发作

(如<48h)是否与长时间发作风险相同[960]。术后 AF 患者 OAC 的适应证和使用时间应当考虑到术后出血

的风险。

13.5.3 术后心房颤动的节律控制治疗

在血流动力学不稳定的患者,推荐复律和考虑使用抗心律失常药物。对将术后 AF 转复为窦性心律,

胺碘酮或维纳卡兰有效[603,950,961]。最近一项中等规模随机试验,将术后 AF 的患者随机分配到使用胺碘酮

进行节律控制或室率控制组,在 60 天随访期期间没有发现住院率有差异[962],支持节律控制的目标应当是

改善术后 AF 的相关症状。对于无症状患者和症状可接受的患者,室率控制或先予抗凝后延期复律是合理

的方法。

妊娠期间的推荐

推荐 推荐

类别

证据

水平

参考

文献

推荐围术期口服β阻滞剂用于预防心脏外科术后 AF。 Ⅰ B 925,928

在血流动力学不稳定的术后 AF 患者,推荐电复律或用抗心律失

常药物以恢复窦性心律。

Ⅰ C

对于心脏外科术后伴有卒中风险的患者,要个体化考虑卒中和出

血风险,应考虑长期抗凝治疗。

Ⅱa B 368,386

对于心脏外科术后的症状性 AF,应考虑用抗心律失常药物尝试

恢复窦性心律。

Ⅱa C

应当考虑围术期使用胺碘酮作预防性治疗,以预防心脏外科术后

AF。

Ⅱa A 905

无症状性术后 AF 应当启动室率控制和抗凝治疗。 Ⅱa B 962

对于没有严重心力衰竭、低血压或严重结构性心脏病的术后 AF

患者,可考虑静脉注射维纳卡兰转复心律。

Ⅱb B 603

AF:心房颤动;

13.6 成人先天性心脏病患者的房性心律失常

房性心律失常(AF、心房扑动、房性心动过速)经常发生于先天性心脏缺陷外科修复术后晚期, 见

于 15-40%的成人先天性心脏病患者(grown-up patients with congenital heart disease ,GUCH)。他们通常

伴有心力衰竭、晕厥、血栓栓塞事件和猝死[963-967]。其病理生理学机制复杂,与心肌肥厚、纤维化、低氧

血症、慢性血流动力学超负荷、手术瘢痕、补片相关。此外,与传导通路相关的原发畸形可能导致折返性

房性和室性心动过速、心脏阻滞和窦房结功能障碍[963]。几乎在任何外科术后均可见涉及心房切口或心房

补片的大折返性房性心动过速或不典型心房扑动。

13.6.1 成人先天性心脏病患者房性心律失常的一般治疗

传统的卒中危险因素应当用于指导 GUCH 合并 AF 患者的长期抗凝决策。此外,当存在心内补片、紫

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绀、Fontan 姑息手术或系统性右室的 GUCH 患者发生房性心律失常时,应考虑抗凝治疗[968]。可以使用β

阻滞剂、维拉帕米、地尔硫卓和洋地黄。应注意避免心动过缓和低血压。

在 Fontan 手术的患者中,钠通道阻滞剂大约可抑制一半的房性心律失常[969]。胺碘酮更为有效,但是

在相对年轻的人群中,抗心律失常药物长期治疗可产生心外副作用的高风险。心腔内血栓在接受 AF 复律

的 GUCH 患者中常见,但是也可见于房性心动过速或心房扑动[970]。因此,在计划复律前应考虑 TOE 检查

和应用抗凝药物数周[964]。射频消融对 GUCH 患者的症状性房性心律失常可能是一个好的选择,尤其是对

心房扑动和其它大折返性心动过速的患者。介入治疗应当在有充分资质的中心由专业团队进行。

13.6.2 房性心律失常和房间隔缺损

在未手术的房间隔缺损的成人,有 14-22%发生心房扑动和颤动,尤其是在年长患者中[971],可导致心

力衰竭[972]。早期修复可减少但是并不能消除 AF 风险[973]。双心房容量超负荷[974]、肺动脉高压[975]和心房

补片可能的致心律失常作用均促进这些心律失常的发生[976]。应当在卒中风险因素的基础上确定抗凝治

疗。在有阵发性或持续性 AF 病史的患者中,可考虑在房缺修补的同时行 AF 外科手术,或是在介入房间

隔缺损封堵术同时行导管消融术。在小规模房间隔缺损外科术后的患者队列中,显示晚期房性心律失常的

导管消融是有效的[977]。

13.6.3 Fontan 术后的快速性房性心律失常

高达 40%的 Fontan 循环患者存在快速性房性心律失常,可能表现为心房扑动、初发性房性心动过速、

AF 和加速的交界区心律或交界区心动过速,伴或不伴窦房结功能障碍[979]。心房肺动脉吻合的患者(可能

由于心房容量较高,压力负荷较大)和那些早期术后房性心律失常的患者,更有可能发展为长期快速性房

性心律失常[980]。房性心律失常也可以是心房肺动脉吻合阻塞的首发表现,这是一种必须要识别的并发

症。右心房血栓形成在伴有房性心律失常的 Fontan 术后病人常见,需要口服抗凝治疗[981]。在一些患者

中,有效的完全性腔肺动脉连接结合心律失常外科手术可改善心力衰竭症状,减少心律失常复发[969,982],

并且在重复手术的最初几年里,临床上显性房性心律失常复发率低[983-985]。Fontan 患者房性心律失常导管

消融在某些特定患者中已经取得了成功[986]。

13.6.4 法洛氏四联征矫治术后的快速性房性心律失常

在法洛氏四联征修复后,大约 1/3 的患者发生房性心律失常,包括心房内折返性心动过速、局灶性房

性心动过速和 AF[987]。报告涉及三尖瓣环峡部和推定的右心房外科手术瘢痕区域的折返环导致房性心律失

常。

13.7 心房扑动的管理

心房扑动的管理目标与 AF 患者相似[992]。根据可提供的证据基础,心房扑动患者的卒中风险与 AF 患

者并无太多差异[827]。此外,许多诊断为心房扑动的患者会发生 AF[993-995]。因此,在心房扑动患者中的抗

凝药物应用与 AF 患者相似。使用 AF 患者中相同的药物可以控制心房扑动的室率,但是通常很难达到目

标。氟卡尼、普罗帕酮、多非利特和静脉注射伊布利特可用于心房扑动复律。这些药物应当联合室率控制

药物使用,以避免缓慢扑动波至心室的 1:1 传导。伊布利特转复心房扑动比转复 AF 更为有效,而维纳卡

兰转复典型心房扑动几乎无效[996,997]。心房扑动电复律可以使用低于 AF 的能量(50-100J)[998,999]。通过起

搏器导线或心内或经食道导管进行心房超速起搏可将心房扑动转复为窦性心律[1000,1001]。复律或超速起搏前

后抗凝和 TOE 的使用与 AF 类似。

对峡部依赖性右房扑动(包括常见的逆钟向心房扑动和少见的顺钟向心房扑动)进行三尖瓣环峡部消

融恢复和维持窦性心律,成功率为 90-95%[1002]。在特定患者中,也可以降低 AF 复发率[1003,1004],有助于预

防住院[1004,1005]。峡部消融安全性与抗心律失常药物相当,而效果更好,推荐用于复发性心房扑动[585-

587,713]。左心房大折返性心动过速消融较为复杂,成功率较低,复发率较高[1006,1007]。

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对成人先天性心脏病患者的推荐

推荐 推荐

类别

证据

水平

参考

文献

在 40 岁之前应考虑关闭房间隔缺损以减少心房扑动和颤动的机

会。

Ⅱa C 971,972,9

74

对于需要外科关闭房间隔缺损和有症状性房性心律失常病史的

患者,应考虑在手术时行 AF 消融。

Ⅱa C 204,988,9

89

对于有症状性 AF 和先天性心脏缺损矫治修复术适应证的患者,

应考虑 Cox 迷宫手术。所有此类外科手术均应在有经验的中心进

行。

Ⅱa C 988,990

对于有心内补片、紫绀、Fontan 姑息手术或系统性右室并发 AF、

心房扑动或心房内折返性心动过速病史的所有成人患者,应当考

虑口服抗凝剂。在所有其他先天性心脏病伴有 AF 的患者,如果

CHA2DS2VASC 评分≥1 分,应考虑抗凝治疗。

Ⅱa C 968

先天性心脏病合并房性心律失常的患者,如在有经验的中心实

施,可以考虑导管消融。

Ⅱb C 991

对先天性心脏病患者,可以考虑在复律前 3 周抗凝治疗并进行经

食道超声心动图检查。

Ⅱb C 964,970,9

88,990

AF:心房颤动;CHA2DS2-VASc: 充血性心力衰竭,高血压,年龄≥75 岁(2 分),糖尿病,卒中

(2 分),血管疾病,年龄 65-74 岁,性别(女性);GUCH:患有先天性心脏病的成人;OAC:

口服抗凝剂;TOE:经食道超声心动图。

心房扑动管理的推荐

推荐 推荐

类别

证据

水平

参考

文献

对心房扑动患者,推荐根据与 AF 相同的危险因素进行抗凝治疗。 Ⅰ B 827

根据当地的可及性和经验而定,可以考虑心房超速起搏替代电复

律。 Ⅱa B 1000,100

1

推荐对抗心律失常药物治疗失败患者的典型心房扑动进行三尖

瓣环峡部消融,或者对于有意愿的患者可作为一线治疗。 Ⅰ B 158

如果在 AF 消融前记录到心房扑动,应考虑三尖瓣环峡部消融作

为 AF 消融程序的一部分。 Ⅱa C

AF:心房颤动。

14.患者参与,教育和自我管理

14.1 以患者为中心的照护

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自主、知情的患者对长期治疗的依从性更好,很有可能的是,慢性病如 AF 的长期管理将受益于知情

的患者,这些患者知道他们在疾病管理过程中的责任[328]。共同决策[747]和以患者为中心组织的关怀有助于

确保治疗的依从性,并赋予患者权利,尊重患者个体的意愿、需求和价值观(见 7.2 章)[326,1008,1009]。作用

积极的患者往往具有更好的健康结局和护理经验,并且自我管理可以被认为是一种中间终点[1010]。

14.2 一体化患者教育

教育是知情的先决条件,涉及患者和以患者为中心的照护。然而,患者常缺乏 AF 相关知识,即使在

那些接受了口头和书面信息的患者中也是如此[32,1011,1012],这表明需要进一步发展结构化的患者教育。已开

发了几种主要针对口服抗凝剂的患者信息工具 [1013-1016]。本工作组开发了一种 AF 患者的专用应用程序,

以支持病人获取信息和教育。了解患者对 AF 及其管理的认知和态度,可以改善房颤的管理和相关的结局[1017]。这包括针对疾病、症状认知、治疗、AF 可纠正的危险因素以及自我管理活动的个体化患者教育[1018,1019]。

14.3 自我管理和共同决策

自我管理主要集中于管理疾病的任务,例如坚持治疗方案或改善生活方式(如戒烟或减肥)[1020]。这

需要对治疗方式和目标的理解[350]。在一个多学科团队中,各专业的卫生专业人员可以指导这种互动,在

这一过程中,通过沟通,信任和相互尊重促进患者的参与[1021]。应当考虑共同决策作为决策过程的常规组

成部分[747],在合适的情况下,由决策辅助工具支持[1022]。目前已有一体化教育、参与和共同决策的照护模

式[1023],可能对 AF 的管理尤其有价值。

患者参与、教育和自我管理的推荐

推荐 推荐

类别

证据

水平

参考

文献

推荐在 AF 管理的所有阶段进行个体化患者教育,以支持患者对

AF 的理解和改善管理。

Ⅰ C 1014,101

7

应当考虑患者参与照护过程,鼓励自我管理和负责改变生活方

式。

Ⅱa C 328,1010

应考虑共同决策,以确保管理措施是基于可用的最佳证据并适合

患者的需求、价值观和意愿。

Ⅱa C

AF:心房颤动。

15 证据缺口

AF 管理的一些领域(如口服抗凝剂),得到多项有充分把握度的随机试验优秀证据的支持。其他领

域,诸如节律控制治疗、AF 的一体化管理和生活方式改变明确需要开发证据,而如室率控制领域迫切需

要更好的研究以支持未来的指南。这里,我们确定了需要进一步研究的领域。

15.1 引起心房颤动的主要健康因素

心房颤动在不同的患者中病因不同。需要在不同 AF 患者群体的主要病因方面(以及电生理机制)进

行更多的研究[176,1024]。这类研究应当考虑与 AF 伴随的共病,以及具有不同病理生理学类型 AF 患者对治

疗反应所表现的特征。

15.2 有多少心房颤动需要治疗?

技术进步允许使用患者控制的 ECG 设备、智能手机和各种其他设备筛查不规则脉率。这些可能对检

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出无症状的未确诊 AF 有用[157]。仍需要有充分把握度的研究,来评价此类技术的诊断准确性、在不同人群

中的诊断阳性率、导致卒中风险的房性心律失常的最短持续时间类型、以及 ECG 筛查对转归的影响。

15.3 心房高频事件和抗凝需求

所有 OAC 获益的信息均来自于通过 ECG 诊断 AF 的患者。技术进步使得在植入了器械和心房导线的

患者中能够检出 AHRE。此类患者卒中风险增加,但是不清楚他们是否可从 OAC 中获益。评价 OAC 在

AHRE 患者中的对照试验正在进行中,将提供在这些患者中抗栓治疗的最佳证据。

15.4 特殊人群中的卒中风险

应当研究几个特殊 AF 群体以更好地确定其 AF、卒中和其他 AF 相关并发症风险(如只有一项卒中危

险因素的患者和非高加索人患者)。混杂因素(如不同的心血管合并疾病的治疗)可能有助于解释报告的

AF 发生率、AF 患病率和 AF 并发症的差异。这也适用于性别对 AF 患者的影响[47]。

15.5 严重慢性肾病患者中的抗凝治疗

没有在肌酐清除率<30mL/min 的患者中测试过 NOACs,对 OAC 在透析或其他形式肾脏替代治疗患

者的效果证据很少。需要评价 OAC 在严重 CKD 患者中的研究,以明确在这一高卒中和出血风险的患者群

体中的最佳管理。

15.6 左心耳封堵预防卒中

临床实践中,LAA 封堵最常见的理由是预期高出血风险,次要理由是对 OAC 有禁忌[459]。遗憾的是,

未曾在此类人群中测试过 LAA 封堵器。此外,没有在有出血风险的患者中对比 LAA 封堵器与 NOAC 治

疗,也没有与经胸腔镜 LAA 夹闭进行对比。这显然需要进行适当设计和有把握度的试验,以确定与

NOAC 治疗相比,在具有抗凝的相对或绝对禁忌的患者和/或患有缺血性卒中患者的抗凝治疗中,LAA 封

堵器的临床作用。

15.7 心房颤动患者出血或卒中事件后的抗凝治疗

每年至少 2%抗凝治疗的 AF 患者将会发生严重的出血事件。观察性数据表明,即使在颅内出血事件

后,也可重新启动 OAC[460,484]。迫切需要对照研究评价不同抗凝治疗和卒中预防措施,以对发生出血事件

并常常导致停用 OAC 的患者提供最佳管理的证据。一些研究(例如 APACHE-AF[心房颤动患者在抗凝相

关颅内出血后应用阿哌沙班、抗血小板药物或不使用抗栓药物的比较] [1025])正在进行中,但是仍需要有充

分把握度的试验。同样,需要前瞻性收集在卒中或颅内出血后,开始应用(重新启动)OAC 后卒中预防和

出血风险的数据。

15.8 非急诊复律的抗凝治疗和最佳时间

基于回顾性数据,以前关于安全时间窗的推荐,在≤48h 内的新发 AF 作为无保护复律的金标准,可

以进行复律。然而,已有新证据表明,在 AF 发作<24h 甚至 12h 的患者中复律前进行抗凝将更为安全[642,647,1026-1028]。需要进一步的研究确定这一临床情况的安全性范围。

15.9 心房颤动患者中卒中或短暂性脑缺血发作的竞争性病因

前瞻性 RCTs 已经证实,与支架植入术相比,在症状性颈内动脉严重狭窄的患者中颈动脉内膜剥脱术

的优势[1029]。由于剥脱术将 OAC 和抗血小板药物联合治疗的需求降至最低[1030],这一方法对 AF 患者降低

出血风险具有吸引力。然而,这些研究很少包括 AF 患者。在一项大型观察性研究中,院内死亡、术后卒

中和心脏并发症的复合终点在接受颈动脉支架的 AF 患者中((457/7668;6.0%)高于剥脱术的患者

(4438/51 320;8.6%;P <0.0001)[1031]。尽管调整了基线风险,这可能只是反映了每个手术涉及患者的

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类型,仍需要进一步的随机化研究证实对伴有颈动脉疾病 AF 患者的最佳治疗策略。

15.10 生物瓣膜(包括经导管主动脉瓣植入)和非风湿性瓣膜病瓣膜病患者的抗凝

在生物瓣膜置换术(包括经导管瓣膜置换术)后的第一个月的最佳抗栓治疗仍然未知。VKAs 仍然是

术后早期的唯一选择;NOACs 可能具有同样的保护作用。在没有 AF 的患者中,许多中心单独使用血小板

抑制剂。根据 ROCKET-AF 试验的亚组分析以及卢瓦尔河谷 AF 项目数据[1033],NOACs 在中度主动脉瓣狭

窄的患者中可能具有同 VKAs 同样的效果[1032]。更多的数据将有助于证实这些观察[1034]。尚未评价 NOACs

在风湿性二尖瓣疾病中的安全性和有效性,应当对此进行研究。

15.11 “成功”导管消融后的抗凝治疗

鉴于 AF 的长期复发率,工作组推荐在“成功”导管消融后的 AF 患者中继续应用 OAC。无论如何,

观察性数据表明与其他 AF 患者相比,在 AF 导管消融后,卒中风险可能较低。正在进行的 EAST-AFNET4

试验将告诉我们,在大多数常见情况下,是否节律控制治疗能够降低抗凝的 AF 患者的卒中风险。此外,

似乎应当有评估在“成功”导管消融后,OAC 治疗终止时间的对照试验的一席之地。

15.12 室率控制药物的比较

尽管在 AF 患者中,室率控制治疗很常见,比较室率控制治疗的有力数据仍不足,大多数研究是小型

的非对照研究,只进行了短期随访。一些研究正在进行[如 RATE-AF(永久性心房颤动中室率控制治疗评

估)[559]],将研究不同室率控制药物的潜在获益,以及有助于进行个体化应用室率控制的特征或生物标记

物,及在特定患者群体中特异药物的不良事件表现。

15.13 持续性和长程持续性 AF 的导管消融

虽然最近的一些随机化研究支持在持续性 AF 和长程持续性 AF 患者中进行导管或外科消融[1042],但仍

明确需要更多的、以有充分把握度的随机试验数据来评估这种干预措施。

15.14 重复导管消融的最佳技术

PVI 出现成为 AF 导管消融的最重要靶点。尽管已经出现了更多不同的消融技术,但其在接受首次消

融,包括持续性 AF 患者中的价值仍有疑问[735,1042]。许多患者需要多次导管消融,这种干预通常遵循当地

或操作者特定的方案,没有明确的证据支持选择消融靶点或干预措施。对于需要二次消融手术的患者,临

床明确需要确定最佳的方法。

15.15 维持窦性心律的联合治疗

即使在有经验的中心进行,首次成功导管消融后的随访中,也有许多患者出现症状性 AF 复发。这些

患者通常需要抗心律失常药物治疗。评价导管消融后 AF 复发患者中不同的节律控制措施的数据出奇地缺

乏。此类研究似乎是合理和可行的。

15.16 心房颤动患者中节律控制治疗能够带来预后获益吗?

节律控制治疗(导管消融、新型抗心律失常药物)的进展和长期观察分析表明节律控制治疗在抗凝的

AF 患者中可能有预后获益。正在进行的试验,如 CABANA 和 EAST-AFNET4 将提供这一重要问题的初步

答案,但是需要更多的数据,包括外科消融技术的试验。

15.17 经胸腔镜“单独”心房颤动外科治疗

十年前报告了微创心外膜消融外科手术治疗孤立性心房颤动[1035]。后来这种手术已经演变为完全胸腔

镜手术[1036],损伤扩展至完全性左心房迷宫术[822]。迫切需要使用标准程序进行随机化试验,以明确胸腔镜

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AF 消融的获益和风险,并进一步支持 AF 心脏团队的决策。

15.18 外科切除左心耳

心胸外科医师进行 LAA 切除已有十余年,但是目前仍缺乏比较切除或不切除左心耳的情况下,缺血

性卒中发生率的前瞻性随机化研究。LAAOS(左心耳封堵研究)Ⅲ,当前正在随机入组需心脏手术的 AF

患者,将接受心外科手术的 AF 患者分为同时进行左心耳封堵或不进行封堵组[467]。在获得早期阳性的观察

性数据之后,还需要更多的数据来确定胸腔镜切除术的安全性和有效性[1037]。

15.19 伴随进行心房颤动外科手术

需要有充分把握度的随机化试验,采用统一的消融方案和能源,进行系统随访,以评价伴随进行的

AF 手术治疗症状性 AF 患者的获益和风险。一项消融方案不一致的长期随访 RCT 将很快发表[1038]。此类

试验将帮助 AF 心脏团队确定个体患者的最佳治疗,包括药物和手术治疗 AF 的完整措施的选择。

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16. 指南中做和不做的信息

推荐 类别 a 水平 b

AF 诊断和筛查的推荐

确定 AF 诊断需要 ECG 证实 Ⅰ B

推荐在>65 岁的患者中,通过触诊脉搏或 ECG 节律记录条图对 AF 进行机会性筛查。 Ⅰ B

在 TIA 或缺血性卒中患者中,推荐短期 ECG 记录后,进行连续至少 72 小时的心电图

监测筛查 AF。 Ⅰ B

推荐规律询问起搏器和 ICD 记录的心房高频事件(AHRE)。AHRE 患者应当接受进一

步的 ECG 监测,以便在启动 AF 治疗前证实 AF。 Ⅰ B

AF 一般管理的推荐

推荐在 AF 管理的所有阶段进行个体化患者教育,以支持患者对 AF 的理解和改善管

理。 Ⅰ C

推荐对所有 AF 患者,进行充分的心血管评估,包括确切的病史、仔细的临床检查和合

并疾病的评估 Ⅰ C

推荐在临床实践和研究中,使用改良的 EHRA 症状量表,量化 AF 相关的症状。 Ⅰ C

推荐对所有 AF 患者使用经胸超声心动图以指导治疗。 Ⅰ C

推荐对所有 AF 患者,通过血清肌酐或肌酐清除率评估肾功能,以检出肾脏疾病并支持

对 AF 治疗药物剂量的调整。 Ⅰ A

AF 卒中预防的推荐

推荐对 AF 患者用 CHA2DS2-VASc 评分进行卒中风险的预测。 Ⅰ A

推荐对所有 CHA2DS2-VASc 评分大于等于 2 分的男性 AF 患者,口服抗凝治疗以预防

血栓栓塞。 Ⅰ A

推荐对所有 CHA2DS2-VASc 评分大于等于 3 分的女性 AF 患者,口服抗凝治疗以预防

血栓栓塞。 Ⅰ A

对于适合用 NOAC(阿哌沙班,达比加群,依度沙班,或利伐沙班)的 AF 患者,当启

动口服抗凝时,推荐 NOAC,优于维生素 K 拮抗剂。 Ⅰ A

对于中到重度二尖瓣狭窄或置入机械心脏瓣膜的 AF 患者,推荐用维生素 K 拮抗剂治

疗(INR2.0-3.0 或更高)进行卒中预防。 Ⅰ A

不推荐 NOACs(阿哌沙班,达比加群,依度沙班和利伐沙班)用于机械性心脏瓣膜

(证据水平 B)或中至重度二尖瓣狭窄(证据水平 C)的患者。

(有害) B C

当患者使用维生素 K 拮抗剂治疗时,应当尽可能保持较高的治疗范围内时间(TTR)

并严密监测 Ⅰ A

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联用口服抗凝剂和血小板抑制剂增加出血风险,在没有血小板抑制剂适应证的 AF 患者

中应当避免。

(有害) B

在没有其他额外卒中危险因素的男性或女性 AF 患者中,不推荐抗凝或抗血小板治疗用

于卒中预防。

(有害) B

不推荐抗血小板单药治疗用于 AF 患者的卒中预防,无论卒中风险如何 Ⅲ

(有害) A

在左心耳外科封堵或切除术后,为预防卒中,推荐有风险的 AF 患者继续抗凝治疗。 Ⅰ B

不推荐在启动维生素 K 拮抗剂治疗前进行基因检测。 Ⅲ

(无益) B

在严重活动性出血的 AF 患者中,推荐中断口服抗凝治疗直至去除潜在出血病因 Ⅰ C

NOACs 应避免用于妊娠和计划妊娠的妇女。 Ⅲ

(有害) C

对于心房扑动的患者,推荐根据 AF 使用的相同风险评估进行抗栓治疗。 Ⅰ B

对于抗心律失常药物治疗失败的典型房扑患者,推荐采用腔静脉三尖瓣峡部消融,或

考虑患者意愿作为一线治疗。 Ⅰ B

推荐对于发生了 AF 的肥厚型心肌病患者,终生口服抗凝药物以预防卒中。 Ⅰ B

不推荐对于 AF 患者发生缺血性卒中后即刻予以肝素或低分子肝素抗凝治疗。 Ⅲ

(有害) A

如果 INR 在 1.7 以上(或对于用达比加群的患者,如果活化部分凝血活酶时间超出正

常范围),不推荐使用重组组织性纤溶酶原激活剂进行全身溶栓治疗。

(有害) C

在 TIA 或卒中后,不推荐 OAC 和抗血小板联合治疗。 Ⅲ

(有害) B

AF 室率控制的推荐

推荐β阻滞剂、地高辛、地尔硫卓或维拉帕米用于 LVEF≥40%的 AF 患者的室率控

制。 Ⅰ B

推荐β阻滞剂和/或地高辛用于 LVEF≥40%的 AF 患者的室率控制。 Ⅰ B

对永久性 AF 患者(如不计划尝试恢复窦性心律),抗心律失常药物不应常规用于室率

控制。

(有害) A

AF 的节律控制

推荐节律控制治疗用于改善 AF 患者的症状。 Ⅰ B

对于有症状的持续性或长程持续性 AF 患者,推荐 AF 心脏复律(电复律或药物复律)

作为节律控制治疗的一部分。 Ⅰ B

在没有缺血性或结构性心脏病病史的患者中,推荐氟卡尼、普罗帕酮或维纳卡兰用于

新发 AF 药物复律 Ⅰ A

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在有缺血性和/或结构性心脏病病史的患者中,推荐胺碘酮用于 AF 的药物复律。 Ⅰ A

对于 AF/心房扑动转复,推荐在复律前至少进行 3 周有效抗凝治疗。 Ⅰ B

当计划早期转复时,推荐经食道超声心动图(TOE)排除心脏内血栓替代操作前抗凝治

疗。 Ⅰ B

选择 AAD 需要仔细评估,考虑存在的合并疾病、心血管危险和潜在的严重致心律失常

作用、心外毒性作用、患者意愿和症状负荷。 Ⅰ A

推荐决奈达隆、氟卡尼、普罗帕酮或索他洛尔用于预防左室功能正常、没有病理性左

室肥厚患者的症状性 AF 复发。 Ⅰ A

推荐决奈达隆用于预防没有心力衰竭的稳定性冠心病患者的症状性 AF 复发 Ⅰ A

推荐胺碘酮用于预防心力衰竭患者的症状性 AF 复发。 Ⅰ B

不推荐长 QT 间期(>0.5s)或有明显窦房结病变或 AV 结功能不良而没有植入功能性

永久起搏器的患者接受 AAD 治疗。

(有害) C

在使用抗心律失常药物(胺碘酮、决奈达隆、氟卡尼、普罗帕酮、索他洛尔)仍有症

状性 AF 复发的患者,以及愿接受进一步节律控制治疗的患者,由经过适当训练的电生

理专家操作,在有经验的电生理中心实施,推荐对症状性阵发性 AF 患者进行导管消融

以改善 AF 症状。

Ⅰ A

对于很轻或没有潜在心脏病的患者,不推荐用 ACEI 或 ARB 进行阵发性 AF 的二级预

防。

(无益) B

推荐中等程度规律的体力活动以预防 AF,但应告知运动员长期持续高强度体育运动可

能促发 AF Ⅰ A

ACE:血管紧张素转换酶抑制剂;AF:心房颤动; AHRE:心房高频事件;ARB:血管紧张素受体

拮抗剂;CHA2DS2-VASc: 充血性心力衰竭,高血压,年龄≥75 岁(2 分),糖尿病,卒中(2 分),血

管疾病,年龄 65-74 岁,性别(女性);ECG:心电图;EHRA:欧洲心律学会;ICD:植入式心律转复除

颤器;INR:国际标准化比值;LV:左室的;LVH:左室肥厚;NOAC:非维生素 K 拮抗剂类口服抗凝

剂;OAC:口服抗凝剂;TIA:短暂性脑缺血发作;TOE:经食道超声心动图;TTR:治疗范围时间;

VKA:维生素 K 拮抗剂

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17. 心房颤动患者管理的简短总结

17. 心房颤动患者管理的简短总结

根据 2016ESC 与 EACTS 合作开发的房颤管理指南,专家组提出了 17 条诊断和管理房颤患

者的简要指导原则:

(1)对于 AF 高危人群,特别是卒中幸存者和老年人,使用 ECG 筛查 AF。

(2)在启动治疗前通过 ECG 证实 AF。

(3)对所有 AF 患者进行评估,包括临床评估、ECG 和超声心动图以寻找潜在病因,如高

血压、心力衰竭、瓣膜性心脏病和其他情况。

(4)对 AF 患者提供个体化信息和教育,以鼓励他们支持 AF 管理。

(5)对所有合适的 AF 患者提倡生活方式改变以使其管理更为有效。

(6)充分治疗潜在的心血管疾病,如对有明显瓣膜性心脏病的 AF 患者进行瓣膜修复或置

换,治疗心力衰竭,或管理高血压及其他因素。

(7)基于 CHA2DS2VASc 评分,对所有 AF 患者使用口服抗凝剂,除非患者属卒中低危,

或有抗凝治疗真正的禁忌证。

(8)心房扑动患者的抗凝治疗与 AF 患者相同。对症状性心房扑动患者进行峡部消融。

(9)对于所有使用口服抗凝药的房颤患者,要降低全部可改变的出血危险因素,例如治疗高

血压、缩短并用抗血小板药物和非甾体类抗炎药的时间并降低治疗强度、治疗贫血并消除失

血原因、对于在用 VKA 的患者,保持稳定的 INR 值和减少酒精摄入。

(10)检查所有房颤患者的心室率,使用控制心室率的药物达到宽松的心室率控制。

(11)使用改良的欧洲心律学会的症状量表,评估所有房颤患者的房颤相关症状。无论何时

患者有房颤相关的症状,就要通过调整室率控制治疗和提供抗心律失常药物、心脏转复、导

管或外科消融,以缓解症状。

(12)基于药物安全性特征选择抗心律失常药物,当抗心律失常药物无效时,应考虑导管或

外科消融。

(13)对 AF 患者不要进行常规基因检测,除非怀疑遗传性心脏病。

(14)不要使用抗血小板药物治疗来预防 AF 患者的卒中。

(15)对于卒中风险高的 AF 患者,不要永久停用口服抗凝治疗,除非由多学科团队做出这

一决定。

(16)对于无症状 AF 患者及永久性 AF 患者,不要使用节律控制治疗。

(17)如果没有进行抗凝,就不要进行复律或导管消融,除非经食道超声心动图检查排除了

心房血栓。

18. 网页附录

在 2016 ESC AF 指南的网页附录中有三个附加的网页图和两个附加的网页表格,在欧洲心脏病杂志网

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页及 ESC 网页((www.escardio.org/guidelines)上可获得。

19. 附录

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