心力衰竭與心律失常

1、心力衰竭與心律失常,楊向軍蘇州大學(xué)附屬第一醫(yī)院,心力衰竭的心律失常,心力衰竭患者：心動(dòng)過(guò)緩、心動(dòng)過(guò)速、房性心律失常的危險(xiǎn)逐步增加心房纖顫的發(fā)生率約20－30%40% 猝死室性快速性心律失常室性緩慢性心律失常心力衰竭治療藥物可能導(dǎo)致緩慢性心律失常,心力衰竭心律失常的發(fā)生機(jī)理,,,,,,,心房電重構(gòu),,右房電標(biāo)測(cè),,冠狀竇遠(yuǎn)端起搏左房-右房電傳導(dǎo),,,,右房傳導(dǎo)速度,心衰心房肌有效不應(yīng)期和AF持續(xù)時(shí)間的改變,,,,,心衰心房肌

2、Ito的改變,心力衰竭心房肌IK的改變,,心力衰竭心房肌Ica-L的變化,,心力衰竭心房肌INCX的變化,,心力衰竭心房肌IK1的變化,,心衰心房肌細(xì)胞,Ito密度下降IK密度下降Ica密度下降INCX增加,,動(dòng)作電位時(shí)程延長(zhǎng)心房復(fù)極離散加大細(xì)胞內(nèi)蓋超載,,心律失常,心室電重構(gòu),,心衰心室肌細(xì)胞動(dòng)作電位時(shí)程延長(zhǎng),,正常和心衰心室肌動(dòng)作電位,,ctl,Ctl+Cs+,HF+Cs+,HF,心衰心室肌后除極電位,,(Cs+),心衰心

3、室肌EAD的發(fā)生率,,Cs+,Cs+,Copyright ©1999 American Physiological Society,Nuss, H. B. et al. Am J Physiol Heart Circ Physiol 277: H80-H91 1999,后除極電位致觸發(fā)活性,normal myocytes with low-Ca2+ cesium-Tyrode solution,Failing myocyte

4、s with low-Ca2+ cesium-Tyrode solution,心衰心室肌DAD與觸發(fā)活性,,Failing myocytes with low-Ca2+ cesium-Tyrode solution,,TTX (10 µM) did not inhibit SD,心衰心室肌INa,,心力衰竭心室肌鉀流,,Ito通道動(dòng)力學(xué)特征,,Ito單通道電流,,心衰心室肌IK的改變,,心衰心室肌IKs的改變,,

5、心衰心室肌IKr的改變,,IK1單通道電導(dǎo)無(wú)差別,,Arrhythmogenesis and Contractile Dysfunction in Heart Failure,,發(fā)生率90%,發(fā)生率0%,心衰心室肌If的表達(dá),,心衰心室肌細(xì)胞,Ito密度下降IK密度下降Ik1密度下降If的表達(dá),,動(dòng)作電位時(shí)程延長(zhǎng)心房復(fù)極離散加大早期后除極電位自律性增加,,心律失常,心力衰竭心律失常的治療,,心力衰竭房性心律失常的治療,,AF

6、FIRM研究,,AFFIRM研究,,AFFIRM研究,,AFFIRM研究,,AFFIRM研究,,,心衰患者>18 歲; EF <40%; NYHA心功能分級(jí) II-IV級(jí),,,906 人死亡 (事件記錄),纈沙坦40 mg Bid 逐漸增量至160 mg Bid,安慰劑,隨機(jī)分組,,,Cohn et al. J Card Fail 1999;5:155-160,,,Val-HeFT 試驗(yàn)設(shè)計(jì),藥物

7、 患者人數(shù) 百分比（%）ACEI 4641 93利尿劑 4299 86地高辛 3372 67?-受體阻滯劑 1784 36,1.0,0.9,0.8,0.6,,,危險(xiǎn)降低 13.3%P= 0.009,病死率和病殘率

8、聯(lián)合終點(diǎn),0,無(wú)事件發(fā)生率,纈沙坦,安慰劑,,,3,6,9,12,21,18,15,24,27,隨機(jī)分組的時(shí)間（月）,0.7,Val-HeFT亞組分拆： Valsartan 組，AF發(fā)生率顯著↓ 新發(fā)生房顫危險(xiǎn)降低35% ESC 2003 Cir. Sept.29 2003,AT1受體拮抗劑與心房顫動(dòng),Nakas

9、hima H等, Circulation 2000;101:2612,動(dòng)物實(shí)驗(yàn)證明，Candesartan(ARB)可預(yù)防快速起搏引起的心房不應(yīng)期縮短，可能有利于預(yù)防AF的發(fā)生。 狗（20），反復(fù)間斷高頻心房起搏（800次/分），測(cè)AERP前后比較。,AngII靜滴 生理鹽水靜滴 Candesartan靜滴 Captopril靜滴,AERP 顯著縮短（P<0.01）,AERP 無(wú)變化（NS）,AERP 顯

10、著縮短（P<0.01）,AERP 無(wú)變化（NS）,,AT1受體拮抗劑與心房顫動(dòng),Kumagai K 等 JACC.2003;18:2197,狗(20),400次/分 右房刺激5周, 誘發(fā)AF。Candesartan (10mg/kg1d) VS placebo 電刺激前1周開(kāi)始，連續(xù)共6周,結(jié)果：ARB組比安慰劑組平均AF持續(xù)時(shí)間顯著縮短(411 ± 301 VS 1333 ± 725

11、秒，p<0.01)ARB組心肌間質(zhì)纖維化積分顯著較安慰劑組低(7 ± 2% VS 16 ± 1%，p<0.001),,心力衰竭室性心律失常的治療,,ATMA會(huì)萃分析，包括了8個(gè)心梗后試驗(yàn)(包括EMIAT和CAMIAT) 5個(gè)HF試驗(yàn)(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試驗(yàn),MADIT II,Moss AJ ( Uni of

12、 Rochester )：前瞻性隨機(jī)對(duì)照試驗(yàn)（1998.01-2001.11）美國(guó)，71中心；歐洲，5中心 1200多病例目的：,對(duì)心肌梗死后心功能不全患者，在常規(guī)藥物治療基礎(chǔ)上，植入ICD能否降低總死亡率,MADIT II 的試驗(yàn)設(shè)計(jì),SCD-HeFT: The Sudden Cardiac Death in Heart Failure Trial American College of Cardiology 8 Marc

13、h 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

14、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 deat

15、h 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

16、 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

17、? 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

18、 52%, 48%? 6 minute walk 1130 ft (840, 1360)? Diabetes 30%? CABG and/or Perc. Revasc. 37%? H/O Hypertension 56%? H/O

19、Hyperlipidemia 53%? H/O AF 15%? H/O NSVT 23%? ECG QRS duration 112 ms (96, 140), 41%> =120 ms,,SCD-He