心力衰竭与心律失常文档资料.ppt
心力衰竭的心律失常,心力衰竭患者：心动过缓、心动过速、房性心律失常的危险逐步增加心房纤颤的发生率约2030%40%猝死室性快速性心律失常室性缓慢性心律失常心力衰竭治疗药物可能导致缓慢性心律失常,心力衰竭心律失常的发生机理,心房电重构,右房电标测,冠状窦远端起搏左房-右房电传导,右房传导速度,心衰心房肌有效不应期和AF持续时间的改变,心衰心房肌Ito的改变,心力衰竭心房肌IK的改变,心力衰竭心房肌Ica-L的变化,心力衰竭心房肌INCX的变化,心力衰竭心房肌IK1的变化,心衰心房肌细胞,Ito密度下降IK密度下降Ica密度下降INCX增加,动作电位时程延长心房复极离散加大细胞内盖超载,心律失常,心室电重构,心衰心室肌细胞动作电位时程延长,正常和心衰心室肌动作电位,ctl,Ctl+Cs+,HF+Cs+,HF,心衰心室肌后除极电位,(Cs+),心衰心室肌EAD的发生率,Cs+,Cs+,Copyright 1999 American Physiological Society,Nuss,H.B.et al.Am J Physiol Heart Circ Physiol 277:H80-H91 1999,后除极电位致触发活性,normal myocytes with low-Ca2+cesium-Tyrode solution,Failing myocytes with low-Ca2+cesium-Tyrode solution,心衰心室肌DAD与触发活性,Failing myocytes with low-Ca2+cesium-Tyrode solution,TTX(10M)did not inhibit SD,心衰心室肌INa,心力衰竭心室肌钾流,Ito通道动力学特征,Ito单通道电流,心衰心室肌IK的改变,心衰心室肌IKs的改变,心衰心室肌IKr的改变,IK1单通道电导无差别,Arrhythmogenesis and Contractile Dysfunction in Heart Failure,发生率90%,发生率0%,心衰心室肌If的表达,心衰心室肌细胞,Ito密度下降IK密度下降Ik1密度下降If的表达,动作电位时程延长心房复极离散加大早期后除极电位自律性增加,心律失常,心力衰竭心律失常的治疗,心力衰竭房性心律失常的治疗,AFFIRM研究,AFFIRM研究,AFFIRM研究,AFFIRM研究,AFFIRM研究,心衰患者18 岁;EF 40%;NYHA心功能分级 II-IV级,906 人死亡(事件记录),缬沙坦40 mg Bid 逐渐增量至160 mg Bid,安慰剂,随机分组,Cohn et al.J Card Fail 1999;5:155-160,Val-HeFT 试验设计,药物 患者人数 百分比（%）ACEI 4641 93利尿剂 4299 86地高辛 3372 67-受体阻滞剂 1784 36,1.0,0.9,0.8,0.6,危险降低 13.3%P=0.009,病死率和病残率联合终点,0,无事件发生率,缬沙坦,安慰剂,3,6,9,12,21,18,15,24,27,随机分组的时间（月）,0.7,Val-HeFT亚组分拆：Valsartan 组，AF发生率显著 新发生房颤危险降低35%ESC 2003 Cir.Sept.29 2003,AT1受体拮抗剂与心房颤动,Nakashima H等,Circulation 2000;101:2612,动物实验证明，Candesartan(ARB)可预防快速起搏引起的心房不应期缩短，可能有利于预防AF的发生。狗（20），反复间断高频心房起搏（800次/分），测AERP前后比较。,AngII静滴 生理盐水静滴 Candesartan静滴 Captopril静滴,AERP 显著缩短（P0.01）,AERP 无变化（NS）,AERP 显著缩短（P0.01）,AERP 无变化（NS）,AT1受体拮抗剂与心房颤动,Kumagai K 等 JACC.2003;18:2197,狗(20),400次/分 右房刺激5周,诱发AF。Candesartan(10mg/kg1d)VS placebo 电刺激前1周开始，连续共6周,结果：ARB组比安慰剂组平均AF持续时间显著缩短(411 301 VS 1333 725 秒，p0.01)ARB组心肌间质纤维化积分显著较安慰剂组低(7 2%VS 16 1%，p0.001),心力衰竭室性心律失常的治疗,ATMA会萃分析，包括了8个心梗后试验(包括EMIAT和CAMIAT)5个HF试验(包括GESICA和CHF-STAT)6553例，胺碘酮降低死亡率13%、降低心律失常猝死率29%,AVID试验,MADIT II,Moss AJ(Uni of Rochester)：前瞻性随机对照试验（1998.01-2001.11）美国，71中心；欧洲，5中心 1200多病例目的：,对心肌梗死后心功能不全患者，在常规药物治疗基础上，植入ICD能否降低总死亡率,MADIT II 的试验设计,SCD-HeFT:The Sudden Cardiac Death in Heart Failure Trial American College of Cardiology 8 March 2004Gust H.BardySeattle Institute for Cardiac Research Seattle,Washington,SCD-HeFT研究背景,CHF can die suddenly from arrhythmia despite the use of proven medical therapies,such as beta-blockade.Two approaches have been developed specifically to prevent sudden death among patients with CHF:therapy with amiodarone and therapy with ICD.Despite findings in earlier clinical trials,the ability of amiodarone to reduce the risk of death among patients with CHF remains uncertain.The ability of an ICD to limit mortality in CHF has been evaluated in small trials focused on patients with nonischemic cardiomyopathy and also remains unproven.Most of the mortality data on amiodarone and ICD therapy have been obtained in clinical trials performed after myocardial infarction in patients without CHF or those with ventricular arrhythmias.,Baseline Enrollment Characteristics CHF duration 24.5 mo(8.1,59.4)LV EF 25.0(20.0,30.0)NYHA II,III 70%,30%Ischemic,non-ischemic 52%,48%6 minute walk 1130 ft(840,1360)Diabetes 30%CABG and/or Perc.Revasc.37%H/O Hypertension 56%H/O Hyperlipidemia 53%H/O AF 15%H/O NSVT 23%ECG QRS duration 112 ms(96,140),41%=120 ms,SCD-HeFT亚组分析,SCD-HeFT亚组分析,SCD-HeFT亚组分析,SCD-HeFT结论,在扩张型心肌病和冠心病心衰患者（心功II或III级，EF=35%），常规药物治疗的年死亡率为7.2%加用胺碘酮不降低死亡率ICD使死亡率下降23%（P=0.007）,谢 谢！,
