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1、心力衰竭合并心房颤动 CRT与射频消融携手应对,长河医院 吴培俊,心力衰竭（心衰）和心房颤动（房颤）是21世纪心血管疾病领域里两种新的流行病。两者关系密切，常常并存，其发病率和死亡率往往非常高，且有不断增加的趋势，已成为当前社会中最主要的公共健康问题。,2,心衰与房颤之间的关系,相同的人口学特征：发病率随年龄的增长而增加共同的危险因子：高血压，糖尿病，心肌梗死，瓣膜性心肌病等互为因果：,3,心衰,房颤,促进/维持,引发,左房压力升高，交感神经激活，心房扩大，心房肌功能丧失，心脏传导系统损伤,心房心肌和电重构,影响冠状动脉血供，血流动力学障碍，射血分数降低,左房收缩功能丧失，房室失同步，RR间期
2、不规则,4,最新指南建议,关于心室再同步化的临床试验所涵盖的大多是窦律患者；对患永久性房颤合并左室收缩功能降低的患者，若其QRS120ms，大部分证据显示房室结消融后能够从双室起搏获益；CRT对于射血分数低的房颤患者疗效尤为显著。,心衰合并房颤患者的心脏再同步化治疗,5,Heart Rhythm, 2012 ， 2012 ACCF/AHA/HRS Focused Update of the 2008 Guidelinesfor Device-Based Therapy of Cardiac Rhythm Abnormalities,2012年AHA/ACC/HRS对器械治疗指南进行了更新，其中
3、对于心衰合并房颤的患者，给出了如下总结：,心衰合并房颤患者的心脏再同步化治疗,6,B,最佳药物治疗基础上，房颤心律的患者，如果满足：1）需要心室起搏或符合CRT标准；2）房室结消融或药物治疗控制心率达到接近100%心 室起搏可考虑植入CRT。,Heart Rhythm, 2012 ， 2012 ACCF/AHA/HRS Focused Update of the 2008 Guidelinesfor Device-Based Therapy of Cardiac Rhythm Abnormalities,心衰合并房颤患者的心脏再同步化治疗ESC指南更新,European Heart Journ
4、al 2012 ， ESC Guidelines for the diagnosis and treatmentof acute and chronic heart failure 2012,7,心衰合并房颤患者的心脏再同步化治疗ESC指南更新,European Heart Journal 2012 ， ESC Guidelines for the diagnosis and treatmentof acute and chronic heart failure 2012,8,ESC认为CRT对AF患者的疗效还不是十分明确，有待进一步验证理论依据：MUSTIC：一个小规模，单盲的临床研究 59
5、例患永久性房颤的心衰患者，低心室率，QRS200ms， 心室起搏依赖，交叉设计3个月的传统起搏，3个月的CRT治 疗，主要终点6分钟步行结果没有区别RAFT：一随机对照试验 229例患永久性房颤或房扑患者，或药物控制心室率在休息 时60bpm，6分钟步行测试时90bpm，或行房室结消融术， 远期分析治疗效果和基线节律对比没有显示出有深远意义的 作用。,CRT的循证医学,9,大量大规模临床试验已证实CRT不仅可以显著改善心功能，缓解临床症状，提高患者生活质量，还能逆转心脏重构，可从根本上阻止心衰发生、发展的病理生理进程。 BUT 为达到治疗目的，需要最大程度地起搏双室，同时为保证房室顺序，需要病
6、人必须是窦率，以提高CRT的疗效。,对于房颤患者问题随之而来,房颤是否会影响CRT的疗效？CRT能否减少心衰患者房颤的发生？CRT对治疗心衰合并房颤是否可行有效？对心衰伴慢性房颤患者，如何才能达到最佳治疗？,10,房颤是否会影响CRT的疗效？,11,CARE-HF,813位心衰患者随机分组为CRT组及药物治疗组（入选时排出患有持续性房颤的患者）房颤的发生作为不良事件而被记录最终随访了29.4个月比较两组患者新房颤发生率，以及新房颤发生对CRT结果及疗效的影响,12,Circulation July 4, 2006 Effect of Cardiac Resynchronization on t
7、he Incidence of Atrial Fibrillation in Patients With Severe Heart Failure。,CARE-HF死亡率,13,Circulation July 4, 2006 Effect of Cardiac Resynchronization on the Incidence of Atrial Fibrillation in Patients With Severe Heart Failure。,CRT能够降低死亡率，且CRT的疗效不会因为发生新房颤而改变！,18个月的随访，无论有无房颤，CRT组的患者的左室射血分数，左室收缩末期容积，
8、左室充盈时间等均优于药物治疗组,CARE-HF血液动力学等方面的影响,14,Circulation July 4, 2006 Effect of Cardiac Resynchronization on the Incidence of Atrial Fibrillation in Patients With Severe Heart Failure。,CARE-HF,15,Circulation July 4, 2006 Effect of Cardiac Resynchronization on the Incidence of Atrial Fibrillation in Patient
9、s With Severe Heart Failure。,新房颤的发生：CRT合并药物组：66（409）药物治疗组：58（404） 结论： 虽然CRT没有降低房颤的发生率，但无论病人是否患有房颤，CRT都能明显改善患者预后。,没有区别,CRT能否减少心衰患者房颤的发生？,16,欧洲一项小规模的临床试验,入选84例难治性心衰患者，NYHA心功能分级级进行CRT治疗，随访3个月植入时AF患者32人，窦律患者52人观察CRT治疗后房颤发作次数及房颤负荷。,17,Journal of Cardiovascular Electrophysiology Vol. 17, No. 8, August 200
10、6 Atrial Fibrillation Burden During the Post-Implant Period After CRT Using Device-Based Diagnostics,比较三个月的随访，随着CRT的治疗，发生AF的病人数明显减少,欧洲一项小规模的临床试验,18,Journal of Cardiovascular Electrophysiology Vol. 17, No. 8, August 2006 Atrial Fibrillation Burden During the Post-Implant Period After CRT Using Device
11、-Based Diagnostics,欧洲一项小规模的临床试验,19,Journal of Cardiovascular Electrophysiology Vol. 17, No. 8, August 2006 Atrial Fibrillation Burden During the Post-Implant Period After CRT Using Device-Based Diagnostics,随着CRT治疗，患者的房颤负荷以及发生房颤的病人数量均逐渐减少,美国一项临床试验,回顾性研究，96例已植入CRT的患者，NYHA心功能IIIIV 级的慢性心衰患者，LVEF 35%, QR
12、S 130 ms,其中91例患者植入时为窦律，5例患者为房颤经药物转换为窦律随访6个月，其中CRT应答者54例，无应答者42例观察房颤发作率及房颤负荷。,20,PACE 2007 Cardiac Resynchronization Therapy Response is Associated with Shorter Duration of Atrial Fibrillation,美国一项临床试验,21,PACE 2007 Cardiac Resynchronization Therapy Response is Associated with Shorter Duration of Atri
13、al Fibrillation,对比CRT有应答及无应答两组患者入选时的特性基本一致,美国一项临床试验,22,PACE 2007 Cardiac Resynchronization Therapy Response is Associated with Shorter Duration of Atrial Fibrillation,美国一项临床试验,23,PACE 2007 Cardiac Resynchronization Therapy Response is Associated with Shorter Duration of Atrial Fibrillation,对比CRT有应答及
14、无应答两组患者入选时的特性基本一致,结论: CRT应答能够缩短房颤负荷。,CRT对治疗心衰合并房颤是否可行有效？,24,一项前瞻性临床研究,入选263例心衰患者，QRS 120 ms,心功能分级IIIIV 级, LVEF35%，其中慢性房颤96例，窦律167例随访3个月和12个月评价两组患者超声心动及临床指标，包括左室重构逆转，NYHA心功能分级，6min步行距离，生活质量评分，LVEF，二尖瓣返流，1年住院率等同时比较两组患者远期死亡率,25,The American Journal of Cardiology 2007 Comparison of Usefulness of Cardiac
15、 Resynchronization Therapy in Patients With Atrial Fibrillation and Heart Failure Versus Patients With Sinus Rhythm and Heart Failure,一项前瞻性临床研究,26,The American Journal of Cardiology 2007 Comparison of Usefulness of Cardiac Resynchronization Therapy in Patients With Atrial Fibrillation and Heart Fail
16、ure Versus Patients With Sinus Rhythm and Heart Failure,一项前瞻性临床研究,27,The American Journal of Cardiology 2007 Comparison of Usefulness of Cardiac Resynchronization Therapy in Patients With Atrial Fibrillation and Heart Failure Versus Patients With Sinus Rhythm and Heart Failure,CRT治疗能使心衰合并房颤的患者同样受益！,
17、一项前瞻性临床研究,28,The American Journal of Cardiology 2007 Comparison of Usefulness of Cardiac Resynchronization Therapy in Patients With Atrial Fibrillation and Heart Failure Versus Patients With Sinus Rhythm and Heart Failure,慢性房颤组与窦律组1年因心衰住院率均明显下降，分别为84%和90%，两组长期死亡率几乎相等。心衰合并房颤的患者应该进行CRT治疗！,对心衰伴慢性房颤患者,
18、如何才能达到最佳治疗？,29,治疗方案,通过优化程控参数提高房颤患者的CRT疗效CRT结合房室结消融术PAVE研究MILOS研究环肺静脉电隔离结合CRT,30,优化程控参数,对于心衰伴房颤患者，如果心率控制稳定，常规程控即可保证双室起搏比例如果心室率控制不佳，则起搏器有如下功能可以帮助提高双室起搏比例： AMS 自动模式转换 DDT 触发,31,优化程控参数- AMS自动模式转换,发生房性心动过速时，起搏模式由DDD/R自动转换为DDI/RAMS基本频率：当起搏器发生模式转换时，有一个可分开程控的起搏频率 AMS基本频率临床目的:用一个增加的心室起搏频率以补偿心房贡献丧失使AT/AF期间增加的
19、心室起搏频率能最大程度减少快的、不规则的心室传导，促进双室起搏,32,优化程控参数- AMS自动模式转换,AMS的临床意义 R-R间期的变化更小，从而减轻患者症状 更高的频率增加心脏输出，更大程度确保了双室起搏，使患者有更好的血液动力学,33,优化程控参数- DDT触发,DDT/R模式提供了存在自身R波或PVC时的触发起搏，以促进双室起搏DDT 和 VVT 模式T = 触发如果脉冲发生器看见一个自身事件，那么将启动一个输出脉冲对感知事件的处理，与VVI相反在触发起搏中，两个心室的脉冲都会被发放在触发起搏中，无论程控值，室间延迟是“同步的”(LV先10ms),34,优化程控参数- DDT触发,D
20、DT的临床意义：可确保接近100%的双室起搏在房颤伴不稳定的传导期间（心率变化范围很大）能确保双室起搏（BV）,35,治疗方案,通过优化程控参数提高房颤患者的CRT疗效CRT结合房室结消融术PAVE研究MILOS研究环肺静脉电隔离结合CRT,36,CRT结合房室结消融术PAVE研究,37,J Cardiovasc Electrophysiol 2005 Left Ventricular-Based Cardiac Stimulation Post AV NodalAblation Evaluation (The PAVE Study),植入前患者评估,随机分组（n=184）,消融+右室起搏(n
21、=81)（SJM单腔起搏器）,消融+双室起搏(n=103)（SJM三腔起搏器）,入选标准：慢性房颤30天，房室结消融后需起博治疗，LVEF 0.460.16，83%NYHA Class II or III。,术后4周内程控,基本频率80ppm，以降低多形性室速的风险,4周后随访,恢复正常起搏频率，打开频率应答传感器,6周后随访,3个月随访,6个月随访,此后每6个月随访,终点：评价6min步行时间，生活质量，LVEF,两组病人的6-minute步行距离均有显著提高，但是6个月时右室起搏组的步行距离减少，双室起搏组仍然稳定,PAVE研究,38,J Cardiovasc Electrophysiol
22、 2005 Left Ventricular-Based Cardiac Stimulation Post AV NodalAblation Evaluation (The PAVE Study),6-minute hallway walk test,BV,RV,PAVE研究,39,J Cardiovasc Electrophysiol 2005 Left Ventricular-Based Cardiac Stimulation Post AV NodalAblation Evaluation (The PAVE Study),LVEF,基线时两组LVEF相同，双室起搏组一致稳定右室起搏组在
23、6周时降低3.1%，6个月时降低3.7%6个月时双室起搏组明显优于右室起搏组,PAVE研究,40,J Cardiovasc Electrophysiol 2005 Left Ventricular-Based Cardiac Stimulation Post AV NodalAblation Evaluation (The PAVE Study),EF 45%,EF 45%,p=0.02,LVEF低的患者，双室起搏明显优于右室起搏,PAVE研究,41,J Cardiovasc Electrophysiol 2005 Left Ventricular-Based Cardiac Stimulat
24、ion Post AV NodalAblation Evaluation (The PAVE Study),NYHA I,NYHA II, III,p0.01, RV vs. BV,NYHA心功能分级 II, III 级的患者 双室起搏明显优于右室起搏,PAVE研究,42,J Cardiovasc Electrophysiol 2005 Left Ventricular-Based Cardiac Stimulation Post AV NodalAblation Evaluation (The PAVE Study),结论:PAVE试验证实了房颤患者进行房室结射频消融后，双心室再同步化起搏较
25、单纯的右室起搏治疗能够显著性提高6min步行时间和LVEF，尤其在收缩功能受损和心衰患者中获益更加明显。,PAVE研究,43,1，Pacing Clin Electrophysiol. 1997 Feb;20(2 Pt 1):343-8Ventricular fibrillation and sudden death after radiofrequency catheter ablation of the atrioventricular junction,房室结消融的风险/并发症:心室起搏依赖房室结消融的不可逆性使得患者必须要永久起搏房室结消融后起搏频率设置不当有可能引发恶性室性心律失常房
26、室结消融认为阻断了房室的正常传导功能，设置慢的心室起搏频率或是较慢的心室逸搏节律有可能导致恶性室性心律失常甚至猝死，这是房室结消融可能产生的并发症（发生率约6%1）恶性室性心律失常的发生可以通过消融后即刻程控一个临时的较快的起搏频率来预防,MILOS研究,入选1285例患者，其中1042例窦律，243例房颤（19%），房颤组中125例采用药物控制心室率，118例房室结消融随访34个月对比心衰患者的全因死亡率和心源性死亡率，评价房室结射频消融对心衰合并房颤患者CRT治疗长期生存率的影响,44,European Heart Journal (2008) Long-term survival in
27、patients undergoing cardiac resynchronization therapy: the importance of performing atrio-ventricular junction ablation in patients with permanent atrial fibrillation,MILOS研究,45,European Heart Journal (2008) Long-term survival in patients undergoing cardiac resynchronization therapy: the importance
28、of performing atrio-ventricular junction ablation in patients with permanent atrial fibrillation,房颤组与窦律组患者全因死亡率和心源性死亡率非常接近,MILOS研究,46,European Heart Journal (2008) Long-term survival in patients undergoing cardiac resynchronization therapy: the importance of performing atrio-ventricular junction abl
29、ation in patients with permanent atrial fibrillation,房颤两个亚组中，与抗心律失常药物相比，房室结消融能够显著提高CRT心衰患者的生存率。,MILOS研究,47,European Heart Journal (2008) Long-term survival in patients undergoing cardiac resynchronization therapy: the importance of performing atrio-ventricular junction ablation in patients with perm
30、anent atrial fibrillation,MILOS研究,48,European Heart Journal (2008) Long-term survival in patients undergoing cardiac resynchronization therapy: the importance of performing atrio-ventricular junction ablation in patients with permanent atrial fibrillation,CRT治疗有效的患者比例,将LVESV（左室收缩末容积）降低 10%定义为CRT治疗有效
31、,结论：心衰合并房颤的患者进行CRT治疗时，同时辅以房室结射频消融是一种非常重要的手段。与抗心律失常药物控制心室率相比，能够降低心衰的死亡率。,CRT合并房室结消融疗法总结,CRT对于HF患者的疗效是确切的，但合并AF的患者从CRT获益仍存在一定的障碍：首先对于快心室率的患者无法保证合适的双室起搏比例，经常出现的融合或假性融合波会影响到CRT的疗效；其次，AF还有可能增加不恰当电击的风险，增加心衰住院率乃至死亡率。房室结消融术则使得房颤患者能够确保其双室起搏近100%，有效提高了CRT的反应，降低误放电的风险。但同时，房室结消融的不可逆性使得患者必须要心室永久起搏，对于HF的患者双室起搏则是优
32、于单纯右室起搏的。因此,我们可以得出这样的结论：CRT与房室结射频消融术的联合治疗是目前对于HF伴AF的患者有效的治疗方法.,49,Heart failure2013 Recent advances in management of atrial ibrillation in patients with heart failure,治疗方案,通过优化程控参数提高房颤患者的CRT疗效CRT结合房室结消融术PAVE研究MILOS研究环肺静脉电隔离结合CRT,50,环肺静脉电隔离-A Meta-analysis,51,Circ Arrhythm Electrophysiol 2009 Pulmona
33、ry Vein Isolation for the Maintenance of Sinus Rhythm in Patients With Atrial Fibrillation : A Meta-Analysis of Randomized, Controlled Trials,这是一个荟萃分析：分析了5个关于对比环肺静脉消融和最佳药物治疗房颤的试验，肺静脉消融术后12个月维持阵发性房颤不再发生的累积优势比是药物治疗的16倍,环肺静脉电隔离-A Meta-analysis,52,Circ Arrhythm Electrophysiol 2009 Pulmonary Vein Isolati
34、on for the Maintenance of Sinus Rhythm in Patients With Atrial Fibrillation : A Meta-Analysis of Randomized, Controlled Trials,肺静脉消融能够降低因心源性原因导致的住院率,环肺静脉电隔离-A Meta-analysis,53,Circ Arrhythm Electrophysiol 2009 Pulmonary Vein Isolation for the Maintenance of Sinus Rhythm in Patients With Atrial Fibri
35、llation : A Meta-Analysis of Randomized, Controlled Trials,在12个月的随访中，有17%的患者接受了一次重复肺静脉消融术51%的非消融治疗组的患者接受了消融治疗（这种交叉治疗是被允许的）,环肺静脉电隔离疗法总结,54,荟萃分析证明了PVI对于阵发性房颤的疗效PVI的疗效：1年维持窦律的患者为75%，是抗心律失常药物疗效的2倍。PVI可以降低2/3的心源性住院率 。并发症：PVI也存在一定的术后并发症的风险：包括中风，穿孔，肺静脉狭窄等，但这些事件的发生概率极低。复发率：以上5个试验，1年之内重复进行一次PVI手术的患者达17%。,Cir
36、c Arrhythm Electrophysiol 2009 Pulmonary Vein Isolation for the Maintenance of Sinus Rhythm in Patients With Atrial Fibrillation : A Meta-Analysis of Randomized, Controlled Trials,Pulmonary Vein Antrum Isolation vs AV Node Ablation with Bi-Ventricular Pacing,55,PABA-CHF,Heart Rhythm, Vol 9, No 8S, A
37、ugust Supplement 2012 Managing atrial fibrillation in the CRT patient: Controversy or consensus?,56,PABA-CHF,随机，双盲 入选：81例心衰伴房颤患者， NYHA心功能分级为级，没有室间传导延迟（即QRS宽度在90ms左右），其中55%患者患阵发性房颤，45%为持续性房颤 随访6个月 主要终点：6min步行，LVEF，生活质量,European Journal of Heart Failure 9 (2007) 9297 Clinical trials update from the Am
38、erican Heart Association 2006: OAT, SALT 1 and 2, MAGIC, ABCD, PABA-CHF, IMPROVE-CHF, and percutaneous mitral annuloplasty,57,PABA-CHF,结论：PVI组6个月随访内维持窦律的患者占72%，联合抗心律失常药物治疗可增加至90%，患者LVEF及6min步行显著改善,尤其是阵发性房颤的患者。试验结果偏向于PVI组，但还有待继续探索的是PVI对于左室功能紊乱及室间传导延迟的患者（典型CRT适应症患者）的疗效,European Journal of Heart Failur
39、e 9 (2007) 9297 Clinical trials update from the American Heart Association 2006: OAT, SALT 1 and 2, MAGIC, ABCD, PABA-CHF, IMPROVE-CHF, and percutaneous mitral annuloplasty,58,小结,以上临床试验对肺静脉电隔离治疗阵发性房颤的疗效得出了肯定的结论但仍缺乏大量临床依据，需进一步探讨,Heart Rhythm, Vol 9, No 8S, August Supplement 2012 Managing atrial fibri
40、llation in the CRT patient: Controversy or consensus?,59,综上所述,对于心衰合并房颤的患者治疗策略：个体化心衰合并房颤患者的CRT疗效明确，但选择哪种控制心室率的方法存在差异不同心室率控制策略：药物治疗，房室结消融，环肺静脉电隔离等治疗原则：尽可能确保CRT的疗效确保最大化的双室起搏减少以及尽量最小化不恰当的快速心律失常的治疗,Heart Rhythm, Vol 9, No 8S, August Supplement 2012 Managing atrial fibrillation in the CRT patient: Controv
41、ersy or consensus?,60,综上所述,Heart Rhythm, Vol 9, No 8S, August Supplement 2012 Managing atrial fibrillation in the CRT patient: Controversy or consensus?,确定双室起搏比例,通过机器的诊断功能以及Hoter等,持续性房颤,阵发性房颤,房室结消融AV Node Ablation,肺静脉电隔离Pulmonary Vein Antrum Isolation,心衰伴慢性房颤患者的推荐治疗方案,THANKS!,References,Heart Rhythm
42、, 2012 ， 2012 ACCF/AHA/HRS Focused Update of the 2008 Guidelinesfor Device-Based Therapy of Cardiac Rhythm AbnormalitiesEuropean Heart Journal 2012 ， ESC Guidelines for the diagnosis and treatmentof acute and chronic heart failure 2012Circulation July 4, 2006 Effect of Cardiac Resynchronization on t
43、he Incidence of Atrial Fibrillation in Patients With Severe Heart Failure。Journal of Cardiovascular Electrophysiology Vol. 17, No. 8, August 2006 Atrial Fibrillation Burden During the Post-Implant Period After CRT Using Device-Based DiagnosticsPACE 2007 Cardiac Resynchronization Therapy Response is
44、Associated with Shorter Duration of Atrial FibrillationThe American Journal of Cardiology 2007 Comparison of Usefulness of Cardiac Resynchronization Therapy in Patients With Atrial Fibrillation and Heart Failure Versus Patients With Sinus Rhythm and Heart FailureJ Cardiovasc Electrophysiol 2005 Left
45、 Ventricular-Based Cardiac Stimulation Post AV Nodal Ablation Evaluation (The PAVE Study)Pacing Clin Electrophysiol. 1997 Feb;20(2 Pt 1):343-8 Ventricular fibrillation and sudden death after radiofrequency catheter ablation of the atrioventricular junctionEuropean Heart Journal (2008) Long-term surv
46、ival in patients undergoing cardiac resynchronization therapy: the importance of performing atrio-ventricular junction ablation in patients with permanent atrial fibrillationEuropace (2012) Cardiac resynchronization therapy after atrioventricular junction ablation for symptomatic atrial fibrillation
47、: a meta-analysisJournal of the American College of Cardiology Vol. 59, No. 8, 2012 AV Junction Ablation in Heart Failure Patients With Atrial Fibrillation Treated With Cardiac Resynchronization TherapyCirc Arrhythm Electrophysiol 2009 Pulmonary Vein Isolation for the Maintenance of Sinus Rhythm in
48、Patients With Atrial Fibrillation : A Meta-Analysis of Randomized, Controlled TrialsHeart Rhythm, Vol 9, No 8S, August Supplement 2012 Managing atrial fibrillation in the CRT patient: Controversy or consensus?European Journal of Heart Failure 9 (2007) 9297 Clinical trials update from the American Heart Association 2006: OAT, SALT 1 and 2, MAGIC, ABCD, PABA-CHF, IMPROVE-CHF, and percutaneous mitral annuloplasty,62,
